rs12938126

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024702.3(ZNF750):c.1725A>G(p.Ala575Ala) 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

Publications

18 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]

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 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)

TBCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1177929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ZNF750	NM_024702.3 link	c.1725A>G	p.Ala575Ala	synonymous_variant	Exon 3 of 3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5 link	c.1318+15655T>C		intron_variant	Intron 13 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF750	ENST00000269394.4 link	c.1725A>G	p.Ala575Ala	synonymous_variant	Exon 3 of 3	1	NM_024702.3	ENSP00000269394.3
TBCD	ENST00000355528.9 link	c.1318+15655T>C		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

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

GnomAD2 exomes

AF:

0.393

AC:

98688

AN:

251314

AF XY:

0.390

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 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

African (AFR)

AF:

0.406

AC:

13589

AN:

33480

American (AMR)

AF:

0.431

AC:

19255

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

10060

AN:

26136

East Asian (EAS)

AF:

0.368

AC:

14617

AN:

39700

South Asian (SAS)

AF:

0.345

AC:

29739

AN:

86258

European-Finnish (FIN)

AF:

0.396

AC:

21127

AN:

53334

Middle Eastern (MID)

AF:

0.389

AC:

2245

AN:

5768

European-Non Finnish (NFE)

AF:

0.411

AC:

456686

AN:

1112006

Other (OTH)

AF:

0.401

AC:

24239

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

29731

59463

89194

118926

148657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14216

28432

42648

56864

71080

<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:

0.401

AC:

60930

AN:

152096

Hom.:

12309

Cov.:

AF XY:

0.399

AC XY:

29643

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.404

AC:

16752

AN:

41488

American (AMR)

AF:

0.422

AC:

6458

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1355

AN:

3470

East Asian (EAS)

AF:

0.359

AC:

1851

AN:

5154

South Asian (SAS)

AF:

0.343

AC:

1653

AN:

4814

European-Finnish (FIN)

AF:

0.395

AC:

4180

AN:

10588

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.403

AC:

27399

AN:

67978

Other (OTH)

AF:

0.394

AC:

832

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1910

3819

5729

7638

9548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.398

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

Jun 09, 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

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.47

PhyloP100

-0.26

PromoterAI

0.046

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over