Variant 3-126461614-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025112.5(ZXDC):c.2048A>G(p.Gln683Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,613,978 control chromosomes in the GnomAD database, including 2 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

ZXDC
NM_025112.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.267

Variant links:

Genes affected

ZXDC (HGNC:28160): (ZXD family zinc finger C) Enables C2H2 zinc finger domain binding activity; LRR domain binding activity; and transcription coactivator activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZXDC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008073062).

BP6

Variant 3-126461614-T-C is Benign according to our data. Variant chr3-126461614-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2348281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZXDC	NM_025112.5 linkuse as main transcript	c.2048A>G	p.Gln683Arg	missense_variant	6/10	ENST00000389709.8	NP_079388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZXDC	ENST00000389709.8 linkuse as main transcript	c.2048A>G	p.Gln683Arg	missense_variant	6/10	1	NM_025112.5	ENSP00000374359	P2	Q2QGD7-1
ZXDC	ENST00000336332.5 linkuse as main transcript	c.2048A>G	p.Gln683Arg	missense_variant	6/6	1		ENSP00000337694	A2	Q2QGD7-2
ZXDC	ENST00000515545.5 linkuse as main transcript	c.1172A>G	p.Gln391Arg	missense_variant, NMD_transcript_variant	6/9	1		ENSP00000426532

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000244

AC:

AN:

249522

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

129

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000125

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.038

DANN

Benign

0.40

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0081

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.090

Sift

Benign

0.33

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0010

B;B

Vest4

0.045

MVP

0.030

MPC

0.093

ClinPred

0.024

GERP RS

-9.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.21

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