Variant 19-53577495-A-G 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.935A>G(p.Asn312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,502 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.437

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=0.028631896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF331	NM_001079906.2 linkuse as main transcript	c.935A>G	p.Asn312Ser	missense_variant	6/6	ENST00000449416.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF331	ENST00000449416.6 linkuse as main transcript	c.935A>G	p.Asn312Ser	missense_variant	6/6	5	NM_001079906.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251468

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1460556

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000967

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000494

AC:

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 02, 2021

The c.935A>G (p.N312S) alteration is located in exon 7 (coding exon 3) of the ZNF331 gene. This alteration results from a A to G substitution at nucleotide position 935, causing the asparagine (N) at amino acid position 312 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.1

DANN

Benign

0.61

DEOGEN2

Benign

0.040

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.30

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

M_CAP

Benign

0.0021

MetaRNN

Benign

0.029

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

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.1

N;N;N;N;N;N;N;N;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

1.3

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

REVEL

Benign

0.10

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.022

B;B;B;B;B;B;B;B;B;B;B;B;B

Vest4

0.081, 0.13, 0.11, 0.12, 0.083, 0.093, 0.086

MVP

0.21

MPC

1.4

ClinPred

0.024

GERP RS

2.8

Varity_R

0.042

gMVP

0.030

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