Genetic Variant ZNF626:p.Glu457Gly (chr19-20624507-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 13/19 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076675.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	NM_001076675.3	MANE Select	c.1370A>G	p.Glu457Gly	missense	Exon 4 of 4	NP_001070143.1	Q68DY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	ENST00000601440.6	TSL:4 MANE Select	c.1370A>G	p.Glu457Gly	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+21177A>G		intron	N/A

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

214000

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

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

African (AFR)

AF:

0.00

AC:

AN:

31628

American (AMR)

AF:

0.00

AC:

AN:

37472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22220

East Asian (EAS)

AF:

0.00

AC:

AN:

33690

South Asian (SAS)

AF:

0.00

AC:

AN:

78386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4598

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1025520

Other (OTH)

AF:

0.00

AC:

AN:

53558

GnomAD4 genome

AF:

0.0000163

AC:

AN:

61258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25508

American (AMR)

AF:

0.00

AC:

AN:

4066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1182

East Asian (EAS)

AF:

0.00

AC:

AN:

1790

South Asian (SAS)

AF:

0.00

AC:

AN:

1726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

22436

Other (OTH)

AF:

0.00

AC:

AN:

746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ExAC

AF:

0.00000832

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

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

PhyloP100

0.21

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

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over