Genetic Variant ZNF626:p.Ser508Thr (chr19-20624355-A-T) – 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.1522T>A(p.Ser508Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S508P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00044 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

ZNF626
NM_001076675.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.472

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=0.06987345).

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.1522T>A	p.Ser508Thr	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.1522T>A	p.Ser508Thr	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+21329T>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

79618

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000437

AC:

575

AN:

1315794

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

290

AN XY:

648202

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

31306

American (AMR)

AF:

0.000481

AC:

AN:

37394

Ashkenazi Jewish (ASJ)

AF:

0.000848

AC:

AN:

22416

East Asian (EAS)

AF:

0.00168

AC:

AN:

31026

South Asian (SAS)

AF:

0.0000954

AC:

AN:

73344

European-Finnish (FIN)

AF:

0.000716

AC:

AN:

44718

Middle Eastern (MID)

AF:

0.000238

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.000400

AC:

408

AN:

1018988

Other (OTH)

AF:

0.000611

AC:

AN:

52394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

79750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

38342

African (AFR)

AF:

0.00

AC:

AN:

27114

American (AMR)

AF:

0.00

AC:

AN:

6048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1808

East Asian (EAS)

AF:

0.00

AC:

AN:

2474

South Asian (SAS)

AF:

0.00

AC:

AN:

2086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

34272

Other (OTH)

AF:

0.00

AC:

AN:

966

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

(source)

DANN

Benign

0.29

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.023

M_CAP

Benign

0.0015

MetaRNN

Benign

0.070

PhyloP100

0.47

Sift4G

Uncertain

0.0020

Vest4

0.13

MVP

0.21

ClinPred

0.12

GERP RS

-1.7

Varity_R

0.039

Mutation Taster

=99/1

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