chr17-82831752-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_024702.3(ZNF750):c.703A>G(p.Met235Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,822 control chromosomes in the GnomAD database, including 25,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2331 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22897 hom. )

Consequence

ZNF750
NM_024702.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.11

Publications

30 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

TBCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019102395).

BP6

Variant 17-82831752-T-C is Benign according to our data. Variant chr17-82831752-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060121.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024702.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF750	NM_024702.3	MANE Select	c.703A>G	p.Met235Val	missense	Exon 2 of 3	NP_078978.2	Q32MQ0
TBCD	NM_005993.5	MANE Select	c.1318+16818T>C		intron	N/A	NP_005984.3
TBCD	NM_001411101.1		c.1267+16818T>C		intron	N/A	NP_001398030.1	A0A804HLI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF750	ENST00000269394.4	TSL:1 MANE Select	c.703A>G	p.Met235Val	missense	Exon 2 of 3	ENSP00000269394.3	Q32MQ0
TBCD	ENST00000355528.9	TSL:1 MANE Select	c.1318+16818T>C		intron	N/A	ENSP00000347719.4	Q9BTW9-1
TBCD	ENST00000684760.1		c.1318+16818T>C		intron	N/A	ENSP00000507696.1	A0A804HJY5

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25600

AN:

151834

Hom.:

2328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0824

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.175

AC:

43914

AN:

251358

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.0824

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.171

AC:

250160

AN:

1461870

Hom.:

22897

Cov.:

AF XY:

0.168

AC XY:

121883

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.132

AC:

4409

AN:

33480

American (AMR)

AF:

0.285

AC:

12730

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3595

AN:

26136

East Asian (EAS)

AF:

0.0738

AC:

2928

AN:

39700

South Asian (SAS)

AF:

0.0584

AC:

5037

AN:

86258

European-Finnish (FIN)

AF:

0.235

AC:

12562

AN:

53412

Middle Eastern (MID)

AF:

0.107

AC:

619

AN:

5768

European-Non Finnish (NFE)

AF:

0.178

AC:

198449

AN:

1112000

Other (OTH)

AF:

0.163

AC:

9831

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14994

29988

44981

59975

74969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6870

13740

20610

27480

34350

<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:

0.169

AC:

25620

AN:

151952

Hom.:

2331

Cov.:

AF XY:

0.169

AC XY:

12514

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.134

AC:

5545

AN:

41412

American (AMR)

AF:

0.232

AC:

3545

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

494

AN:

3466

East Asian (EAS)

AF:

0.0826

AC:

427

AN:

5172

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4824

European-Finnish (FIN)

AF:

0.231

AC:

2441

AN:

10546

Middle Eastern (MID)

AF:

0.106

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.182

AC:

12377

AN:

67964

Other (OTH)

AF:

0.149

AC:

314

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1057

2113

3170

4226

5283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.170

Hom.:

10105

Bravo

AF:

0.170

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.172

AC:

662

ESP6500AA

AF:

0.131

AC:

577

ESP6500EA

AF:

0.178

AC:

1534

ExAC

AF:

0.169

AC:

20541

Asia WGS

AF:

0.0610

AC:

215

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.158

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ZNF750-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0020

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.00092

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.22

PhyloP100

-2.1

PrimateAI

Benign

0.24

PROVEAN

Benign

0.23

REVEL

Benign

0.034

Sift

Benign

0.87

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.019

MPC

0.21

ClinPred

0.0077

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.13

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over