rs536704518

Variant names:

• chr2-27377328-C-G
• rs536704518
• NM_144631.6:c.*217G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-27377328-C-G
• chr2-27377328-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144631.6(ZNF513):​c.*217G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00092 in 695,354 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 0.00080 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (0 hom.)
• Consequence: ZNF513 NM_144631.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.298
• Publications: 0 publications found

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]

SNX17 (HGNC:14979): (sorting nexin 17) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BS2: High AC in GnomAd4 at 122 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF513	NM_144631.6	c.*217G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000323703.11	NP_653232.3
SNX17	NM_014748.4	c.*609C>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000233575.7	NP_055563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF513	ENST00000323703.11	c.*217G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_144631.6	ENSP00000318373.6
SNX17	ENST00000233575.7	c.*609C>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_014748.4	ENSP00000233575.2

Frequencies

GnomAD3 genomes AF: 0.000801 AC: 122 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000954 AC: 518 AN: 543018 Hom.: 0 Cov.: 5 AF XY: 0.000849 AC XY: 249 AN XY: 293416

African (AFR) AF: 0.000260 AC: 4 AN: 15378

American (AMR) AF: 0.000604 AC: 20 AN: 33086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19424

East Asian (EAS) AF: 0.00 AC: 0 AN: 31920

South Asian (SAS) AF: 0.00 AC: 0 AN: 61208

European-Finnish (FIN) AF: 0.00114 AC: 38 AN: 33242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4022

European-Non Finnish (NFE) AF: 0.00135 AC: 424 AN: 314626

Other (OTH) AF: 0.00106 AC: 32 AN: 30112

GnomAD4 genome AF: 0.000801 AC: 122 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000779 AC XY: 58 AN XY: 74488

African (AFR) AF: 0.000337 AC: 14 AN: 41562

American (AMR) AF: 0.000523 AC: 8 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000865

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.78
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs536704518; hg19: chr2-27600195;