Variant 19-53576708-G-C 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.148G>C(p.Ala50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,605,810 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.564

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:

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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=0.033825696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001079906.2 linkuse as main transcript	c.148G>C	p.Ala50Pro	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.148G>C	p.Ala50Pro	missense_variant	6/6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

245880

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133190

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1453682

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722494

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.9

DANN

Benign

0.56

DEOGEN2

Benign

0.058

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

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.0015

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

M_CAP

Benign

0.0014

MetaRNN

Benign

0.034

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.35

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

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.65

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

REVEL

Benign

0.019

Sift

Benign

0.22

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

Sift4G

Benign

0.33

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

Polyphen

0.0

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

Vest4

0.045, 0.052, 0.048, 0.043, 0.044, 0.097

MutPred

0.39

Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);Gain of methylation at K54 (P = 0.0609);

MVP

0.21

MPC

0.78

ClinPred

0.010

GERP RS

-5.4

Varity_R

0.039

gMVP

0.23

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