Genetic Variant NM_032772.6:c.79G>A (chr10-75401341-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032772.6(ZNF503):c.79G>A(p.Gly27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZNF503
NM_032772.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101

Publications

0 publications found

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:

ZNF503-AS2 (HGNC:23525): (ZNF503 antisense RNA 2)

ZNF503-AS2 links:

ENSG00000270087 (HGNC:):

ENSG00000270087 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054995924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032772.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF503	NM_032772.6	MANE Select	c.79G>A	p.Gly27Ser	missense	Exon 1 of 2	NP_116161.2
ZNF503	NR_120651.2		n.576G>A		non_coding_transcript_exon	Exon 1 of 4
ZNF503-AS2	NR_024421.1		n.-187C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF503	ENST00000372524.5	TSL:1 MANE Select	c.79G>A	p.Gly27Ser	missense	Exon 1 of 2	ENSP00000361602.4	Q96F45-1
ZNF503-AS2	ENST00000725121.1		n.182+198C>T		intron	N/A
ZNF503-AS2	ENST00000725138.1		n.106+198C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1387802

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31558

American (AMR)

AF:

0.00

AC:

AN:

35724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35744

South Asian (SAS)

AF:

0.00

AC:

AN:

79238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5158

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078922

Other (OTH)

AF:

0.00

AC:

AN:

57876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

0.0021

BayesDel_noAF

Benign

-0.23

CADD

Benign

2.6

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.27

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.26

PhyloP100

-0.10

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.15

REVEL

Benign

0.24

Sift

Benign

0.81

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.12

MutPred

0.22

Gain of glycosylation at G27 (P = 0.0059)

MVP

0.18

MPC

0.55

ClinPred

0.067

GERP RS

-4.7

PromoterAI

0.020

Neutral

(source)

Varity_R

0.039

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over