Variant 19-20624355-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001076675.3(ZNF626):c.1522T>C(p.Ser508Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0037 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0016 ( 52 hom. )

Failed GnomAD Quality Control

Consequence

ZNF626
NM_001076675.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.472

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018360227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3 linkuse as main transcript	c.1522T>C	p.Ser508Pro	missense_variant	4/4	ENST00000601440.6	NP_001070143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6 linkuse as main transcript	c.1522T>C	p.Ser508Pro	missense_variant	4/4	4	NM_001076675.3	ENSP00000469958	P1	Q68DY1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

286

AN:

77166

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00765

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00171

Gnomad EAS

AF:

0.00711

Gnomad SAS

AF:

0.00595

Gnomad FIN

AF:

0.00728

Gnomad MID

AF:

0.0278

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.00440

GnomAD3 exomes

AF:

0.000916

AC:

218

AN:

237888

Hom.:

AF XY:

0.000910

AC XY:

118

AN XY:

129682

show subpopulations

Gnomad AFR exome

AF:

0.000868

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00157

Gnomad EAS exome

AF:

0.00195

Gnomad SAS exome

AF:

0.000946

Gnomad FIN exome

AF:

0.000150

Gnomad NFE exome

AF:

0.000764

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00162

AC:

2128

AN:

1314070

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1138

AN XY:

647408

show subpopulations

Gnomad4 AFR exome

AF:

0.000960

Gnomad4 AMR exome

AF:

0.00314

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.00381

Gnomad4 SAS exome

AF:

0.00433

Gnomad4 FIN exome

AF:

0.00186

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00370

AC:

286

AN:

77288

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

134

AN XY:

37298

show subpopulations

Gnomad4 AFR

AF:

0.00237

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00171

Gnomad4 EAS

AF:

0.00753

Gnomad4 SAS

AF:

0.00546

Gnomad4 FIN

AF:

0.00728

Gnomad4 NFE

AF:

0.00381

Gnomad4 OTH

AF:

0.00431

Alfa

AF:

0.00641

Hom.:

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

Aug 16, 2021

The c.1522T>C (p.S508P) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a T to C substitution at nucleotide position 1522, causing the serine (S) at amino acid position 508 to be replaced by a proline (P). 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

0.083

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.14

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.0065

M_CAP

Benign

0.0013

MetaRNN

Benign

0.018

MutationTaster

Benign

1.0

Sift4G

Uncertain

0.040

Vest4

0.11

MVP

0.17

ClinPred

0.00056

GERP RS

-1.7

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