rs1528533

Positions:

• chr2-27372889-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014748.4(SNX17):​c.256+149G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,242,830 control chromosomes in the GnomAD database, including 105,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17305 hom., cov: 33)
  • Exomes 𝑓: 0.39 (87917 hom.)
• Consequence: SNX17 NM_014748.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX17	NM_014748.4	c.256+149G>C		intron_variant		ENST00000233575.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX17	ENST00000233575.7	c.256+149G>C		intron_variant		1	NM_014748.4	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69594 AN: 151992 Hom.: 17261 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.392 AC: 427868 AN: 1090720 Hom.: 87917 Cov.: 14 AF XY: 0.391 AC XY: 214893 AN XY: 549606

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.458 AC: 69699 AN: 152110 Hom.: 17305 Cov.: 33 AF XY: 0.457 AC XY: 33985 AN XY: 74352

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.408

Alfa AF: 0.428 Hom.: 1953

Bravo AF: 0.469

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.41

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: rs1528533; hg19: chr2-27595756; COSMIC: COSV52011614; COSMIC: COSV52011614;