Genetic Variant ZNF502:p.Pro69Ser (chr3-44721022-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001134442.3(ZNF502):c.205C>T(p.Pro69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF502
NM_001134442.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.23

Variant links:

Genes affected

ZNF502 (HGNC:23718): (zinc finger protein 502) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation by host of viral process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF502 links:

LOC105377056 (HGNC:):

LOC105377056 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059333146).

BP6

Variant 3-44721022-C-T is Benign according to our data. Variant chr3-44721022-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3476540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF502	NM_001134442.3 link	c.205C>T	p.Pro69Ser	missense_variant	Exon 3 of 3	ENST00000436624.7	NP_001127914.1	Q8TBZ5Q96K08

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF502	ENST00000436624.7 link	c.205C>T	p.Pro69Ser	missense_variant	Exon 3 of 3	2	NM_001134442.3	ENSP00000406469.2	Q8TBZ5
ZNF502	ENST00000296091.8 link	c.205C>T	p.Pro69Ser	missense_variant	Exon 4 of 4	1		ENSP00000296091.4	Q8TBZ5
ZNF502	ENST00000449836.5 link	c.205C>T	p.Pro69Ser	missense_variant	Exon 3 of 3	3		ENSP00000397390.1	Q8TBZ5
ZNF502	ENST00000411443.1 link	c.205C>T	p.Pro69Ser	missense_variant	Exon 3 of 3	3		ENSP00000401717.1	C9JLT3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251306

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135842

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:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727210

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 04, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0010

DANN

Benign

0.25

DEOGEN2

Benign

0.0029

T;T;T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00010

M_CAP

Benign

0.00096

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;L;.

PrimateAI

Benign

0.19

PROVEAN

Benign

0.99

N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.57

T;T;T;T

Sift4G

Benign

0.51

T;T;T;D

Polyphen

0.0

B;B;B;.

Vest4

0.041

MutPred

0.31

Gain of phosphorylation at P69 (P = 0.0261);Gain of phosphorylation at P69 (P = 0.0261);Gain of phosphorylation at P69 (P = 0.0261);Gain of phosphorylation at P69 (P = 0.0261);

MVP

0.014

MPC

0.15

ClinPred

0.012

GERP RS

-6.1

Varity_R

0.019

gMVP

0.083

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