chr17-82831592-G-A

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.863C>T(p.Pro288Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0902 in 1,614,130 control chromosomes in the GnomAD database, including 7,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.069 ( 560 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7301 hom. )

Consequence

ZNF750
NM_024702.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.28

Publications

15 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017530024).

BP6

Variant 17-82831592-G-A is Benign according to our data. Variant chr17-82831592-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060437.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF750	NM_024702.3 link	c.863C>T	p.Pro288Leu	missense_variant	Exon 2 of 3	ENST00000269394.4	NP_078978.2
TBCD	NM_005993.5 link	c.1318+16658G>A		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.863C>T	p.Pro288Leu	missense_variant	Exon 2 of 3	1	NM_024702.3	ENSP00000269394.3
TBCD	ENST00000355528.9 link	c.1318+16658G>A		intron_variant	Intron 13 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10564

AN:

152120

Hom.:

561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0380

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0531

GnomAD2 exomes

AF:

0.0685

AC:

17232

AN:

251484

AF XY:

0.0683

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0712

GnomAD4 exome

AF:

0.0924

AC:

135070

AN:

1461892

Hom.:

7301

Cov.:

AF XY:

0.0901

AC XY:

65561

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0141

AC:

473

AN:

33480

American (AMR)

AF:

0.0285

AC:

1274

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

550

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00875

AC:

755

AN:

86256

European-Finnish (FIN)

AF:

0.148

AC:

7927

AN:

53420

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.107

AC:

119261

AN:

1112012

Other (OTH)

AF:

0.0789

AC:

4767

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9151

18303

27454

36606

45757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4130

8260

12390

16520

20650

<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:

0.0694

AC:

10562

AN:

152238

Hom.:

560

Cov.:

AF XY:

0.0692

AC XY:

5149

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0177

AC:

735

AN:

41574

American (AMR)

AF:

0.0380

AC:

581

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00808

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.142

AC:

1504

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7358

AN:

67980

Other (OTH)

AF:

0.0525

AC:

111

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

481

963

1444

1926

2407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0855

Hom.:

1518

Bravo

AF:

0.0589

TwinsUK

AF:

0.103

AC:

382

ALSPAC

AF:

0.0999

AC:

385

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.105

AC:

904

ExAC

AF:

0.0703

AC:

8536

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0921

EpiControl

AF:

0.0858

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF750-related disorder

Benign:1

Feb 20, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.5

PhyloP100

4.3

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.13

Sift

Benign

0.038

Sift4G

Uncertain

0.0060

Vest4

0.11

ClinPred

0.026

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.065

gMVP

0.41

Mutation Taster

=78/22

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over