rs13472

Positions:

• chr2-27377372-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000323703.11(ZNF513):​c.*173C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 745,638 control chromosomes in the GnomAD database, including 54,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11033 hom., cov: 32)
  • Exomes 𝑓: 0.37 (43434 hom.)
• Consequence: ZNF513 ENST00000323703.11 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0350

Genes affected

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]

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-27377372-G-A is Benign according to our data. Variant chr2-27377372-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 335549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX17	NM_014748.4	c.*653G>A		3_prime_UTR_variant	15/15	ENST00000233575.7	NP_055563.1
ZNF513	NM_144631.6	c.*173C>T		3_prime_UTR_variant	4/4	ENST00000323703.11	NP_653232.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX17	ENST00000233575.7	c.*653G>A		3_prime_UTR_variant	15/15	1	NM_014748.4	ENSP00000233575	P1
ZNF513	ENST00000323703.11	c.*173C>T		3_prime_UTR_variant	4/4	1	NM_144631.6	ENSP00000318373	P4
ZNF513	ENST00000407879.1	c.*173C>T		3_prime_UTR_variant	3/3	1		ENSP00000384874	A1
SNX17	ENST00000537606.5	c.*653G>A		3_prime_UTR_variant	14/14	2		ENSP00000439208

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56880 AN: 151920 Hom.: 11010 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.373 AC: 221545 AN: 593600 Hom.: 43434 Cov.: 6 AF XY: 0.373 AC XY: 118907 AN XY: 318824

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.374 AC: 56933 AN: 152038 Hom.: 11033 Cov.: 32 AF XY: 0.375 AC XY: 27867 AN XY: 74318

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.353

Alfa AF: 0.365 Hom.: 9938

Bravo AF: 0.374

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinitis Pigmentosa, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.76

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: rs13472; hg19: chr2-27600239; COSMIC: COSV52011630; COSMIC: COSV52011630;