Variant 10-75399788-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000372524.5(ZNF503):c.902G>A(p.Gly301Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000416 in 1,443,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G301V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ZNF503
ENST00000372524.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

ZNF503 (HGNC:23589): (zinc finger protein 503) Predicted to enable metal ion binding activity. Involved in G1 to G0 transition involved in cell differentiation; negative regulation of cell population proliferation; and negative regulation of gene expression. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF503 links:

ENSG00000270087 (HGNC:):

ENSG00000270087 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18075553).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF503	NM_032772.6 linkuse as main transcript	c.902G>A	p.Gly301Asp	missense_variant	2/2	ENST00000372524.5	NP_116161.2	Q96F45-1
ZNF503	NR_120651.2 linkuse as main transcript	n.812+1317G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF503	ENST00000372524.5 linkuse as main transcript	c.902G>A	p.Gly301Asp	missense_variant	2/2	1	NM_032772.6	ENSP00000361602.4		Q96F45-1
ENSG00000270087	ENST00000418818.6 linkuse as main transcript	n.142+1317G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000141

AC:

AN:

212976

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

116982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000320

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1443902

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

717692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000829

AC:

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

Dec 07, 2023

The c.902G>A (p.G301D) alteration is located in exon 2 (coding exon 2) of the ZNF503 gene. This alteration results from a G to A substitution at nucleotide position 902, causing the glycine (G) at amino acid position 301 to be replaced by an aspartic acid (D). 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

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

Eigen

Benign

0.035

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.66

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.78

REVEL

Benign

0.088

Sift

Uncertain

0.026

Sift4G

Benign

0.27

Polyphen

0.80

Vest4

0.31

MutPred

0.20

Loss of catalytic residue at G301 (P = 0.0399);

MVP

0.16

MPC

1.2

ClinPred

0.32

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.086

gMVP

0.22

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