2-27378485-C-G

Position:

• chr2-27378485-C-G

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>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. 14/21 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 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
• Clinical Significance: Not reported in ClinVar
• 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=0.08429161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF513	NM_144631.6	c.781G>C	p.Val261Leu	missense_variant	3/4	ENST00000323703.11	NP_653232.3
ZNF513	NM_001201459.2	c.595G>C	p.Val199Leu	missense_variant	2/3		NP_001188388.1
ZNF513	XM_005264143.4	c.277G>C	p.Val93Leu	missense_variant	2/3		XP_005264200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF513	ENST00000323703.11	c.781G>C	p.Val261Leu	missense_variant	3/4	1	NM_144631.6	ENSP00000318373	P4
ZNF513	ENST00000407879.1	c.595G>C	p.Val199Leu	missense_variant	2/3	1		ENSP00000384874	A1
ZNF513	ENST00000491924.1	n.241G>C		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461762 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.99	N;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		0.12	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

LitVar

Other links and lift over

dbSNP: rs61742428; hg19: chr2-27601352;