Variant chr19-53577174-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001079906.2(ZNF331):c.614A>G(p.His205Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.56

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF331	NM_001079906.2 linkuse as main transcript	c.614A>G	p.His205Arg	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.614A>G	p.His205Arg	missense_variant	6/6	5	NM_001079906.2	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.614A>G (p.H205R) 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 614, causing the histidine (H) at amino acid position 205 to be replaced by an arginine (R). 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

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

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

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.37

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

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.96

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

3.7

H;H;H;H;H;H;H;H;H;H;H;H;H

MutationTaster

Benign

0.60

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-7.9

.;D;.;D;D;D;D;.;D;D;.;.;.

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

.;D;.;D;D;D;D;.;D;D;.;.;.

Sift4G

Pathogenic

0.0

.;D;.;D;D;D;D;.;D;D;.;.;.

Polyphen

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D

Vest4

0.62, 0.57, 0.56, 0.56, 0.62, 0.64, 0.61

MutPred

0.73

Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);

MVP

0.96

MPC

1.8

ClinPred

1.0

GERP RS

3.7

Varity_R

0.85

gMVP

0.78

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