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GeneBe

rs12938126

chr17-82830589-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024702.3(ZNF750):c.1725A>G(p.Ala575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,613,896 control chromosomes in the GnomAD database, including 132,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12309 hom., cov: 33)
Exomes 𝑓: 0.40 ( 120393 hom. )

Consequence

ZNF750
NM_024702.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.256
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-82830589-T-C is Benign according to our data. Variant chr17-82830589-T-C is described in ClinVar as [Benign]. Clinvar id is 1177929.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82830589-T-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.256 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF750NM_024702.3 linkuse as main transcriptc.1725A>G p.Ala575= synonymous_variant 3/3 ENST00000269394.4
TBCDNM_005993.5 linkuse as main transcriptc.1318+15655T>C intron_variant ENST00000355528.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF750ENST00000269394.4 linkuse as main transcriptc.1725A>G p.Ala575= synonymous_variant 3/31 NM_024702.3 P1
TBCDENST00000355528.9 linkuse as main transcriptc.1318+15655T>C intron_variant 1 NM_005993.5 P1Q9BTW9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.401
AC:
60871
AN:
151978
Hom.:
12285
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.403
Gnomad AMI
AF:
0.353
Gnomad AMR
AF:
0.423
Gnomad ASJ
AF:
0.390
Gnomad EAS
AF:
0.359
Gnomad SAS
AF:
0.344
Gnomad FIN
AF:
0.395
Gnomad MID
AF:
0.420
Gnomad NFE
AF:
0.403
Gnomad OTH
AF:
0.398
GnomAD3 exomes
AF:
0.393
AC:
98688
AN:
251314
Hom.:
19599
AF XY:
0.390
AC XY:
52936
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.400
Gnomad AMR exome
AF:
0.430
Gnomad ASJ exome
AF:
0.394
Gnomad EAS exome
AF:
0.356
Gnomad SAS exome
AF:
0.342
Gnomad FIN exome
AF:
0.396
Gnomad NFE exome
AF:
0.399
Gnomad OTH exome
AF:
0.402
GnomAD4 exome
AF:
0.405
AC:
591557
AN:
1461800
Hom.:
120393
Cov.:
124
AF XY:
0.402
AC XY:
292294
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.406
Gnomad4 AMR exome
AF:
0.431
Gnomad4 ASJ exome
AF:
0.385
Gnomad4 EAS exome
AF:
0.368
Gnomad4 SAS exome
AF:
0.345
Gnomad4 FIN exome
AF:
0.396
Gnomad4 NFE exome
AF:
0.411
Gnomad4 OTH exome
AF:
0.401
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.401
AC:
60930
AN:
152096
Hom.:
12309
Cov.:
33
AF XY:
0.399
AC XY:
29643
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.404
Gnomad4 AMR
AF:
0.422
Gnomad4 ASJ
AF:
0.390
Gnomad4 EAS
AF:
0.359
Gnomad4 SAS
AF:
0.343
Gnomad4 FIN
AF:
0.395
Gnomad4 NFE
AF:
0.403
Gnomad4 OTH
AF:
0.394
Alfa
AF:
0.398
Hom.:
5661
Bravo
AF:
0.405
Asia WGS
AF:
0.365
AC:
1271
AN:
3478
EpiCase
AF:
0.403
EpiControl
AF:
0.410

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
1.8
Dann
Benign
0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12938126; hg19: chr17-80788465; COSMIC: COSV53961367; API