Variant 19-20624720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001076675.3(ZNF626):c.1157C>T(p.Thr386Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,609,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ZNF626
NM_001076675.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -7.44

Variant links:

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF626 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08841878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3 linkuse as main transcript	c.1157C>T	p.Thr386Met	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6 linkuse as main transcript	c.1157C>T	p.Thr386Met	missense_variant	4/4	4	NM_001076675.3	P1	Q68DY1-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000169

AC:

AN:

248124

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134662

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000135

AC:

197

AN:

1457768

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

725166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.000229

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000191

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000427

Hom.:

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.000467

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.1157C>T (p.T386M) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a C to T substitution at nucleotide position 1157, causing the threonine (T) at amino acid position 386 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.77

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0066

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.063

T;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;.

MutationTaster

Benign

1.0

Sift4G

Uncertain

0.048

D;T

Polyphen

0.99

D;.

Vest4

0.11

MVP

0.30

MPC

0.24

ClinPred

0.051

GERP RS

-1.5

Varity_R

0.022

gMVP

0.013

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