Variant chr10-75398952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000372524.5(ZNF503):c.1738G>A(p.Ala580Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,599,974 control chromosomes in the GnomAD database, including 3 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 3 hom. )

Consequence

ZNF503
ENST00000372524.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028776348).

BS2

High AC in GnomAd4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF503	NM_032772.6 linkuse as main transcript	c.1738G>A	p.Ala580Thr	missense_variant	2/2	ENST00000372524.5	NP_116161.2	Q96F45-1
ZNF503	NR_120651.2 linkuse as main transcript	n.812+2153G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF503	ENST00000372524.5 linkuse as main transcript	c.1738G>A	p.Ala580Thr	missense_variant	2/2	1	NM_032772.6	ENSP00000361602.4		Q96F45-1
ENSG00000270087	ENST00000418818.6 linkuse as main transcript	n.142+2153G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000474

AC:

104

AN:

219576

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

121320

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000582

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.0000714

Gnomad NFE exome

AF:

0.000656

Gnomad OTH exome

AF:

0.000364

GnomAD4 exome

AF:

0.000736

AC:

1065

AN:

1447782

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

546

AN XY:

720074

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.000111

Gnomad4 NFE exome

AF:

0.000864

Gnomad4 OTH exome

AF:

0.000750

GnomAD4 genome

AF:

0.000480

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000593

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000589

AC:

ExAC

AF:

0.000327

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

Feb 11, 2022

The c.1738G>A (p.A580T) 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 1738, causing the alanine (A) at amino acid position 580 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

Benign

0.070

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.10

Eigen_PC

Benign

0.019

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.047

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.2

REVEL

Benign

0.055

Sift

Benign

0.037

Sift4G

Benign

0.39

Polyphen

0.12

Vest4

0.075

MVP

0.11

MPC

0.55

ClinPred

0.021

GERP RS

4.6

Varity_R

0.11

gMVP

0.57

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