17-82831626-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024702.3(ZNF750):c.829G>A(p.Gly277Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,614,036 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 58 hom. )

Consequence

ZNF750
NM_024702.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.15

Publications

8 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060651004).

BP6

Variant 17-82831626-C-T is Benign according to our data. Variant chr17-82831626-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 773594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 643 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF750	NM_024702.3 link	c.829G>A	p.Gly277Arg	missense_variant	Exon 2 of 3	ENST00000269394.4	NP_078978.2	Q32MQ0
TBCD	NM_005993.5 link	c.1318+16692C>T		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
ZNF750	ENST00000269394.4 link	c.829G>A	p.Gly277Arg	missense_variant	Exon 2 of 3	1	NM_024702.3	ENSP00000269394.3		Q32MQ0
TBCD	ENST00000355528.9 link	c.1318+16692C>T		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4		Q9BTW9-1

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

643

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00760

Gnomad OTH

AF:

0.00528

GnomAD2 exomes

AF:

0.00499

AC:

1254

AN:

251488

AF XY:

0.00508

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.00908

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00712

AC:

10414

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

5023

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

33480

American (AMR)

AF:

0.00114

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00175

AC:

151

AN:

86258

European-Finnish (FIN)

AF:

0.00442

AC:

236

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00862

AC:

9585

AN:

1112010

Other (OTH)

AF:

0.00571

AC:

345

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

755

1510

2264

3019

3774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.00423

AC:

643

AN:

152144

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41496

American (AMR)

AF:

0.00137

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00166

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00760

AC:

517

AN:

67990

Other (OTH)

AF:

0.00522

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00657

Hom.:

Bravo

AF:

0.00383

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00602

AC:

731

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00670

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TBCD: BS2; ZNF750: BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.063

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.016

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

1.2

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Uncertain

0.017

Sift4G

Benign

0.068

Polyphen

1.0

Vest4

0.75

MutPred

0.37

Gain of catalytic residue at G277 (P = 0.0084);

MVP

0.043

MPC

0.85

ClinPred

0.039

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.12

gMVP

0.36

Mutation Taster

=97/3

polymorphism

(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

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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