rs61742428

Variant names:

• chr2-27378485-C-A
• NM_144631.6:c.781G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-27378485-C-A
• chr2-27378485-C-G
• chr2-27378485-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144631.6(ZNF513):​c.781G>T​(p.Val261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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)
• Consequence: ZNF513 NM_144631.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.136

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08560994).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ZNF513-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 261 of the ZNF513 protein (p.Val261Leu). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.64	T
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		0.14	T
GERP RS		3.8
Varity_R		0.053
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27601352;