Variant 19-53577075-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.515A>G(p.Asn172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.717

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=0.035930097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2 link	c.515A>G	p.Asn172Ser	missense_variant	Exon 6 of 6	ENST00000449416.6	NP_001073375.1	Q9NQX6A0A024R4J5Q71QC5Q68D63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6 link	c.515A>G	p.Asn172Ser	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.515A>G (p.N172S) 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 515, causing the asparagine (N) at amino acid position 172 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

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.034

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.083

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

M_CAP

Benign

0.0040

MetaRNN

Benign

0.036

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.7

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

PrimateAI

Benign

0.45

PROVEAN

Benign

1.5

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

REVEL

Benign

0.068

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.030

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

Vest4

0.040, 0.083, 0.067, 0.078, 0.043, 0.046, 0.042

MutPred

0.41

Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);

MVP

0.29

MPC

0.50

ClinPred

0.057

GERP RS

2.5

Varity_R

0.037

gMVP

0.023

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over