Variant 19-53576769-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001079906.2(ZNF331):c.209G>A(p.Arg70Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.116

Variant links:

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ZNF331 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043913215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001079906.2 linkuse as main transcript	c.209G>A	p.Arg70Lys	missense_variant	6/6	ENST00000449416.6	NP_001073375.1	Q9NQX6A0A024R4J5Q71QC5Q68D63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6 linkuse as main transcript	c.209G>A	p.Arg70Lys	missense_variant	6/6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251114

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135796

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727146

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:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 21, 2022

The c.209G>A (p.R70K) alteration is located in exon 7 (coding exon 3) of the ZNF331 gene. This alteration results from a G to A substitution at nucleotide position 209, causing the arginine (R) at amino acid position 70 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

-0.39

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.4

DANN

Benign

0.28

DEOGEN2

Benign

0.045

T;T;T;T;T;.;T;T;.;T;T;T;.;T;T;.;T;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.37

.;.;.;.;T;T;.;.;.;.;.;.;T;.;T;T;.;T;.;.

M_CAP

Benign

0.0011

MetaRNN

Benign

0.044

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.23

N;N;N;N;N;.;N;N;.;N;N;N;.;.;.;.;N;.;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.10

.;N;.;N;N;N;N;N;N;.;N;N;N;N;N;N;.;N;.;.

REVEL

Benign

0.014

Sift

Benign

0.94

.;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.;T;.;.

Sift4G

Benign

0.86

.;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.;T;.;.

Polyphen

0.0010

B;B;B;B;B;.;B;B;.;B;B;B;.;.;.;.;B;.;B;B

Vest4

0.053, 0.073, 0.074, 0.072, 0.060, 0.057, 0.10

MutPred

0.42

Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);Gain of ubiquitination at R70 (P = 0.0388);

MVP

0.35

MPC

0.61

ClinPred

0.0086

GERP RS

0.76

Varity_R

0.026

gMVP

0.15

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