2-27377372-G-A

Variant names:

• chr2-27377372-G-A
• rs13472
• NM_144631.6:c.*173C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144631.6(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 NM_144631.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0350
• Publications: 31 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 -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 rank	MANE	Protein	UniProt
ZNF513	NM_144631.6	c.*173C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000323703.11	NP_653232.3
SNX17	NM_014748.4	c.*653G>A		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.*173C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_144631.6	ENSP00000318373.6
SNX17	ENST00000233575.7	c.*653G>A		3_prime_UTR_variant	Exon 15 of 15	1	NM_014748.4	ENSP00000233575.2

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

African (AFR) AF: 0.353 AC: 5851 AN: 16598

American (AMR) AF: 0.527 AC: 18326 AN: 34756

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 6693 AN: 20272

East Asian (EAS) AF: 0.130 AC: 4186 AN: 32310

South Asian (SAS) AF: 0.409 AC: 25734 AN: 62866

European-Finnish (FIN) AF: 0.428 AC: 14409 AN: 33656

Middle Eastern (MID) AF: 0.341 AC: 1417 AN: 4150

European-Non Finnish (NFE) AF: 0.373 AC: 133245 AN: 356950

Other (OTH) AF: 0.365 AC: 11684 AN: 32042

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

African (AFR) AF: 0.363 AC: 15047 AN: 41454

American (AMR) AF: 0.437 AC: 6681 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1143 AN: 3472

East Asian (EAS) AF: 0.154 AC: 797 AN: 5172

South Asian (SAS) AF: 0.415 AC: 2003 AN: 4824

European-Finnish (FIN) AF: 0.428 AC: 4525 AN: 10574

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25688 AN: 67938

Other (OTH) AF: 0.353 AC: 747 AN: 2116

Alfa AF: 0.373 Hom.: 19306

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinitis Pigmentosa, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

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 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
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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