chr17-82832512-G-A

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.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,487,512 control chromosomes in the GnomAD database, including 22,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2308 hom., cov: 32)
Exomes 𝑓: 0.17 ( 20657 hom. )

Consequence

ZNF750
NM_024702.3 5_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.497

Publications

12 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=-0.84).
BP6
Variant 17-82832512-G-A is Benign according to our data. Variant chr17-82832512-G-A is described in ClinVar as [Benign]. Clinvar id is 1227535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF750NM_024702.3 linkc.-58C>T 5_prime_UTR_variant Exon 2 of 3 ENST00000269394.4 NP_078978.2 Q32MQ0
TBCDNM_005993.5 linkc.1318+17578G>A 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.-58C>T 5_prime_UTR_variant Exon 2 of 3 1 NM_024702.3 ENSP00000269394.3 Q32MQ0
TBCDENST00000355528.9 linkc.1318+17578G>A intron_variant Intron 13 of 38 1 NM_005993.5 ENSP00000347719.4 Q9BTW9-1

Frequencies

GnomAD3 genomes
AF:
0.167
AC:
25405
AN:
151974
Hom.:
2305
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.131
Gnomad AMI
AF:
0.239
Gnomad AMR
AF:
0.229
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.0822
Gnomad SAS
AF:
0.0428
Gnomad FIN
AF:
0.231
Gnomad MID
AF:
0.108
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.150
GnomAD4 exome
AF:
0.169
AC:
226190
AN:
1335420
Hom.:
20657
Cov.:
21
AF XY:
0.165
AC XY:
110900
AN XY:
670752
show subpopulations
African (AFR)
AF:
0.129
AC:
4009
AN:
31112
American (AMR)
AF:
0.284
AC:
12467
AN:
43860
Ashkenazi Jewish (ASJ)
AF:
0.137
AC:
3485
AN:
25384
East Asian (EAS)
AF:
0.0736
AC:
2881
AN:
39130
South Asian (SAS)
AF:
0.0511
AC:
4277
AN:
83680
European-Finnish (FIN)
AF:
0.229
AC:
9163
AN:
40096
Middle Eastern (MID)
AF:
0.0995
AC:
552
AN:
5546
European-Non Finnish (NFE)
AF:
0.178
AC:
180183
AN:
1010066
Other (OTH)
AF:
0.162
AC:
9173
AN:
56546
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
9506
19013
28519
38026
47532
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5968
11936
17904
23872
29840
<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:
0.167
AC:
25426
AN:
152092
Hom.:
2308
Cov.:
32
AF XY:
0.167
AC XY:
12411
AN XY:
74358
show subpopulations
African (AFR)
AF:
0.131
AC:
5426
AN:
41468
American (AMR)
AF:
0.230
AC:
3510
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.143
AC:
494
AN:
3466
East Asian (EAS)
AF:
0.0824
AC:
427
AN:
5184
South Asian (SAS)
AF:
0.0427
AC:
206
AN:
4828
European-Finnish (FIN)
AF:
0.231
AC:
2447
AN:
10580
Middle Eastern (MID)
AF:
0.102
AC:
30
AN:
294
European-Non Finnish (NFE)
AF:
0.182
AC:
12356
AN:
67974
Other (OTH)
AF:
0.148
AC:
312
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1078
2156
3234
4312
5390
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
262
524
786
1048
1310
<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:
0.173
Hom.:
3135
Bravo
AF:
0.168
Asia WGS
AF:
0.0600
AC:
210
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
May 15, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.7
DANN
Benign
0.83
PhyloP100
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs12450046; hg19: chr17-80790388; COSMIC: COSV53960652; API