Genetic Variant ZNF503:p.Pro30Arg (chr10-75401331-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032772.6(ZNF503):c.89C>G(p.Pro30Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000617 in 1,457,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000061 ( 0 hom. )

Consequence

ZNF503
NM_032772.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2628376).

BS2

High AC in GnomAdExome4 at 8 AD gene.

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.89C>G	p.Pro30Arg	missense	Exon 1 of 2	NP_116161.2
ZNF503	NR_120651.2		n.586C>G		non_coding_transcript_exon	Exon 1 of 4
ZNF503-AS2	NR_024421.1		n.-197G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF503	ENST00000372524.5	TSL:1 MANE Select	c.89C>G	p.Pro30Arg	missense	Exon 1 of 2	ENSP00000361602.4	Q96F45-1
ZNF503-AS2	ENST00000725121.1		n.182+188G>C		intron	N/A
ZNF503-AS2	ENST00000725138.1		n.106+188G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

137962

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000611

AC:

AN:

1308884

Hom.:

Cov.:

AF XY:

0.00000618

AC XY:

AN XY:

647658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31442

American (AMR)

AF:

0.00

AC:

AN:

35412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24104

East Asian (EAS)

AF:

0.00

AC:

AN:

35828

South Asian (SAS)

AF:

0.00

AC:

AN:

78726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5190

European-Non Finnish (NFE)

AF:

0.00000797

AC:

AN:

1003682

Other (OTH)

AF:

0.00

AC:

AN:

55512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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

AF:

0.00000672

AC:

AN:

148920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72722

show subpopulations

African (AFR)

AF:

0.0000250

AC:

AN:

40066

American (AMR)

AF:

0.00

AC:

AN:

15006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66692

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000213

AC:

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

0.10

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.068

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.81

PhyloP100

3.7

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.27

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.047

Polyphen

0.40

Vest4

0.22

MutPred

0.39

Loss of loop (P = 0.0073)

MVP

0.15

MPC

0.60

ClinPred

0.70

GERP RS

4.8

PromoterAI

0.035

Neutral

(source)

Varity_R

0.085

gMVP

0.55

Mutation Taster

=71/29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over