Variant 12-133010250-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019591.4(ZNF26):c.371G>A(p.Arg124Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000607 in 1,614,028 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 3 hom. )

Consequence

ZNF26
NM_019591.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.151

Variant links:

Genes affected

ZNF26 (HGNC:13053): (zinc finger protein 26) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038351476).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF26	NM_019591.4 linkuse as main transcript	c.371G>A	p.Arg124Lys	missense_variant	4/4	ENST00000328654.10	NP_062537.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF26	ENST00000328654.10 linkuse as main transcript	c.371G>A	p.Arg124Lys	missense_variant	4/4	1	NM_019591.4	ENSP00000333725	P1
ZNF26	ENST00000534834.1 linkuse as main transcript	n.2976G>A		non_coding_transcript_exon_variant	3/3	2
ZNF26	ENST00000540238.5 linkuse as main transcript			downstream_gene_variant		3		ENSP00000443888
ZNF26	ENST00000544181.5 linkuse as main transcript			downstream_gene_variant		3		ENSP00000445494

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.000625

AC:

913

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

456

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000694

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000434

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000688

Hom.:

Bravo

AF:

0.000476

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

Oct 26, 2021

The c.371G>A (p.R124K) alteration is located in exon 4 (coding exon 4) of the ZNF26 gene. This alteration results from a G to A substitution at nucleotide position 371, causing the arginine (R) at amino acid position 124 to be replaced by a lysine (K). 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

0.078

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.8

DANN

Benign

0.68

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.020

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.57

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.021

Sift

Benign

0.50

T;T

Sift4G

Benign

0.93

T;T

Polyphen

0.0

B;.

Vest4

0.071

MutPred

0.38

Gain of methylation at R124 (P = 0.0449);.;

MVP

0.14

ClinPred

0.030

GERP RS

1.1

Varity_R

0.017

gMVP

0.18

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