Genetic Variant ZNF513:p.Val261Leu (chr2-27378485-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144631.6(ZNF513):c.781G>C(p.Val261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V261M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF513
NM_144631.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

Publications

4 publications found

Variant links:

Genes affected

ZNF513 (HGNC:26498): (zinc finger protein 513) The protein encoded by this gene is a possible transcriptional regulator involved in retinal development. Defects in this gene can be a cause of autosomal-recessive retinitis pigmentosa. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ZNF513 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 58
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ZNF513 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08429161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF513	NM_144631.6 link	c.781G>C	p.Val261Leu	missense_variant	Exon 3 of 4	ENST00000323703.11	NP_653232.3	Q8N8E2-1
ZNF513	NM_001201459.2 link	c.595G>C	p.Val199Leu	missense_variant	Exon 2 of 3		NP_001188388.1	Q8N8E2-2
ZNF513	XM_005264143.4 link	c.277G>C	p.Val93Leu	missense_variant	Exon 2 of 3		XP_005264200.1	Q8N8E2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF513	ENST00000323703.11 link	c.781G>C	p.Val261Leu	missense_variant	Exon 3 of 4	1	NM_144631.6	ENSP00000318373.6	Q8N8E2-1
ZNF513	ENST00000407879.1 link	c.595G>C	p.Val199Leu	missense_variant	Exon 2 of 3	1		ENSP00000384874.1	Q8N8E2-2
ZNF513	ENST00000491924.1 link	n.241G>C		non_coding_transcript_exon_variant	Exon 2 of 3	5
ZNF513	ENST00000436006.1 link	c.*246G>C		downstream_gene_variant		2		ENSP00000394226.1	C9JT52

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;.

PhyloP100

0.14

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.064

Sift

Benign

0.66

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.0040

B;.

Vest4

0.20

MutPred

0.38

Gain of relative solvent accessibility (P = 0.0166);.;

MVP

0.20

MPC

0.31

ClinPred

0.12

GERP RS

3.8

Varity_R

0.053

gMVP

0.21

Mutation Taster

=98/2

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.

chr2-27378485-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over