Variant 19-20624507-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001076675.3(ZNF626):c.1370A>G(p.Glu457Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0000015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ZNF626
NM_001076675.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.212

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:

ENSG00000269110 (HGNC:):

ENSG00000269110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1587472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3 linkuse as main transcript	c.1370A>G	p.Glu457Gly	missense_variant	4/4	ENST00000601440.6	NP_001070143.1	Q68DY1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6 linkuse as main transcript	c.1370A>G	p.Glu457Gly	missense_variant	4/4	4	NM_001076675.3	ENSP00000469958.1		Q68DY1-1
ENSG00000269110	ENST00000595094.1 linkuse as main transcript	n.363+21177A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000163

AC:

AN:

61258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000151

AC:

AN:

1326654

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

659040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000195

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000163

AC:

AN:

61258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29528

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000832

AC:

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 12, 2024

The c.1370A>G (p.E457G) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a A to G substitution at nucleotide position 1370, causing the glutamic acid (E) at amino acid position 457 to be replaced by a glycine (G). 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

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.046

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.10

M_CAP

Benign

0.0019

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.71

Sift4G

Uncertain

0.0090

Polyphen

0.84

Vest4

0.16

MutPred

0.49

Loss of ubiquitination at K460 (P = 0.0578);

MVP

0.26

MPC

0.058

ClinPred

0.16

GERP RS

-1.7

Varity_R

0.15

gMVP

0.021

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