Variant rs12938126 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Clinical Significance

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

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]

ZNF750 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

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_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82830589-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.256 with no splicing effect.

BA1

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	Protein	UniProt
ZNF750	NM_024702.3 linkuse as main transcript	c.1725A>G	p.Ala575=	synonymous_variant	3/3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5 linkuse as main transcript	c.1318+15655T>C		intron_variant		ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF750	ENST00000269394.4 linkuse as main transcript	c.1725A>G	p.Ala575=	synonymous_variant	3/3	1	NM_024702.3	ENSP00000269394	P1
TBCD	ENST00000355528.9 linkuse as main transcript	c.1318+15655T>C		intron_variant		1	NM_005993.5	ENSP00000347719	P1	Q9BTW9-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60871

AN:

151978

Hom.:

12285

Cov.:

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

AF:

0.401

AC:

60930

AN:

152096

Hom.:

12309

Cov.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over