chr17-82832566-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024702.3(ZNF750):​c.-112A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 943,716 control chromosomes in the GnomAD database, including 321,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49787 hom., cov: 33)
Exomes 𝑓: 0.83 ( 271911 hom. )

Consequence

ZNF750
NM_024702.3 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.919

Publications

28 publications found
Variant links:
Genes affected
ZNF750 (HGNC:25843): (zinc finger protein 750) This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]
TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]
TBCD Gene-Disease associations (from GenCC):
  • early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 17-82832566-T-G is Benign according to our data. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82832566-T-G is described in CliVar as Benign. Clinvar id is 1237571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF750NM_024702.3 linkc.-112A>C 5_prime_UTR_variant Exon 2 of 3 ENST00000269394.4 NP_078978.2 Q32MQ0
TBCDNM_005993.5 linkc.1318+17632T>G intron_variant Intron 13 of 38 ENST00000355528.9 NP_005984.3 Q9BTW9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF750ENST00000269394.4 linkc.-112A>C 5_prime_UTR_variant Exon 2 of 3 1 NM_024702.3 ENSP00000269394.3 Q32MQ0
TBCDENST00000355528.9 linkc.1318+17632T>G intron_variant Intron 13 of 38 1 NM_005993.5 ENSP00000347719.4 Q9BTW9-1

Frequencies

GnomAD3 genomes
AF:
0.806
AC:
122565
AN:
152086
Hom.:
49752
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.719
Gnomad AMI
AF:
0.848
Gnomad AMR
AF:
0.884
Gnomad ASJ
AF:
0.769
Gnomad EAS
AF:
0.920
Gnomad SAS
AF:
0.687
Gnomad FIN
AF:
0.848
Gnomad MID
AF:
0.775
Gnomad NFE
AF:
0.835
Gnomad OTH
AF:
0.820
GnomAD4 exome
AF:
0.826
AC:
654087
AN:
791512
Hom.:
271911
Cov.:
11
AF XY:
0.820
AC XY:
339552
AN XY:
414070
show subpopulations
African (AFR)
AF:
0.718
AC:
14718
AN:
20492
American (AMR)
AF:
0.917
AC:
32420
AN:
35352
Ashkenazi Jewish (ASJ)
AF:
0.767
AC:
16357
AN:
21322
East Asian (EAS)
AF:
0.902
AC:
31153
AN:
34552
South Asian (SAS)
AF:
0.685
AC:
46553
AN:
67946
European-Finnish (FIN)
AF:
0.844
AC:
30279
AN:
35882
Middle Eastern (MID)
AF:
0.757
AC:
2621
AN:
3464
European-Non Finnish (NFE)
AF:
0.840
AC:
448534
AN:
534078
Other (OTH)
AF:
0.819
AC:
31452
AN:
38424
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
6230
12460
18689
24919
31149
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
6490
12980
19470
25960
32450
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.806
AC:
122659
AN:
152204
Hom.:
49787
Cov.:
33
AF XY:
0.806
AC XY:
60012
AN XY:
74426
show subpopulations
African (AFR)
AF:
0.719
AC:
29855
AN:
41512
American (AMR)
AF:
0.885
AC:
13534
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.769
AC:
2669
AN:
3472
East Asian (EAS)
AF:
0.919
AC:
4740
AN:
5158
South Asian (SAS)
AF:
0.687
AC:
3311
AN:
4822
European-Finnish (FIN)
AF:
0.848
AC:
8994
AN:
10608
Middle Eastern (MID)
AF:
0.779
AC:
229
AN:
294
European-Non Finnish (NFE)
AF:
0.835
AC:
56823
AN:
68020
Other (OTH)
AF:
0.822
AC:
1734
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1224
2448
3672
4896
6120
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
880
1760
2640
3520
4400
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.828
Hom.:
96402
Bravo
AF:
0.808
Asia WGS
AF:
0.792
AC:
2758
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 13, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
6.3
DANN
Benign
0.64
PhyloP100
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Mutation Taster
=153/147
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3744165; hg19: chr17-80790442; API