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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF513	NM_144631.6	MANE Select	c.*173C>T		3_prime_UTR	Exon 4 of 4	NP_653232.3
	SNX17	NM_014748.4	MANE Select	c.*653G>A		3_prime_UTR	Exon 15 of 15	NP_055563.1	Q15036-1
	ZNF513	NM_001201459.2		c.*173C>T		3_prime_UTR	Exon 3 of 3	NP_001188388.1	Q8N8E2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF513	ENST00000323703.11	TSL:1 MANE Select	c.*173C>T		3_prime_UTR	Exon 4 of 4	ENSP00000318373.6	Q8N8E2-1
	SNX17	ENST00000233575.7	TSL:1 MANE Select	c.*653G>A		3_prime_UTR	Exon 15 of 15	ENSP00000233575.2	Q15036-1
	ZNF513	ENST00000407879.1	TSL:1	c.*173C>T		3_prime_UTR	Exon 3 of 3	ENSP00000384874.1	Q8N8E2-2

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

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;