Variant 19-53577603-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001079906.2(ZNF331):c.1043T>C(p.Ile348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17984456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2 link	c.1043T>C	p.Ile348Thr	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.1043T>C	p.Ile348Thr	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1043T>C (p.I348T) alteration is located in exon 7 (coding exon 3) of the ZNF331 gene. This alteration results from a T to C substitution at nucleotide position 1043, causing the isoleucine (I) at amino acid position 348 to be replaced by a threonine (T). 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

0.72

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

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

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.32

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

M_CAP

Benign

0.0036

MetaRNN

Benign

0.18

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.32

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

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.4

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

REVEL

Benign

0.12

Sift

Benign

0.081

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

Sift4G

Uncertain

0.043

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

Polyphen

0.13

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

Vest4

0.21, 0.21, 0.22, 0.21, 0.21, 0.21, 0.21

MutPred

0.52

Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);Loss of stability (P = 0.0021);

MVP

0.15

MPC

1.8

ClinPred

0.63

GERP RS

4.1

Varity_R

0.13

gMVP

0.082

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