Variant 20-25675757-A-T 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_015655.4(ZNF337):c.1531T>A(p.Leu511Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ZNF337
NM_015655.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.665

Variant links:

Genes affected

ZNF337 (HGNC:15809): (zinc finger protein 337) This gene encodes a zinc finger domain containing protein. The function of this protein has yet to be determined. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ZNF337 links:

ZNF337-AS1 (HGNC:):

ZNF337-AS1 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=0.077245146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF337	NM_015655.4 linkuse as main transcript	c.1531T>A	p.Leu511Met	missense_variant	5/5	ENST00000252979.6	NP_056470.1	Q9Y3M9-1A8K5C0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF337	ENST00000252979.6 linkuse as main transcript	c.1531T>A	p.Leu511Met	missense_variant	5/5	1	NM_015655.4	ENSP00000252979.5		Q9Y3M9-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251386

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.000237

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000193

AC:

282

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000171

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Mar 01, 2024

The c.1531T>A (p.L511M) alteration is located in exon 5 (coding exon 4) of the ZNF337 gene. This alteration results from a T to A substitution at nucleotide position 1531, causing the leucine (L) at amino acid position 511 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.018

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.0041

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.39

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.045

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.95

P;P

Vest4

0.12

MVP

0.19

MPC

0.34

ClinPred

0.082

GERP RS

0.023

Varity_R

0.081

gMVP

0.016

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