Variant 19-53577478-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001079906.2(ZNF331):c.918G>C(p.Lys306Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.891

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF331	NM_001079906.2 linkuse as main transcript	c.918G>C	p.Lys306Asn	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.918G>C	p.Lys306Asn	missense_variant	6/6	5	NM_001079906.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251464

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Feb 17, 2024

The c.918G>C (p.K306N) alteration is located in exon 7 (coding exon 3) of the ZNF331 gene. This alteration results from a G to C substitution at nucleotide position 918, causing the lysine (K) at amino acid position 306 to be replaced by an asparagine (N). 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

0.90

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

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

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.38

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

M_CAP

Benign

0.0065

MetaRNN

Uncertain

0.54

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

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

M;M;M;M;M;M;M;M;M;M;M;M;M

MutationTaster

Benign

1.0

D;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.7

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

REVEL

Benign

0.16

Sift

Uncertain

0.0010

.;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

0.23, 0.24, 0.25, 0.25, 0.24, 0.23

MutPred

0.50

Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);Loss of methylation at K306 (P = 0.0026);

MVP

0.72

MPC

1.7

ClinPred

0.99

GERP RS

3.9

Varity_R

0.70

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