rs4665972

Variant names:

• chr2-27375230-T-C
• rs4665972
• NM_014748.4:c.774+77T>C

Variant summary

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

The NM_014748.4(SNX17):​c.774+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,324,074 control chromosomes in the GnomAD database, including 261,075 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 0.68 (37070 hom., cov: 30)
  • Exomes 𝑓: 0.61 (224005 hom.)
• Consequence: SNX17 NM_014748.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX17	NM_014748.4	c.774+77T>C		intron_variant	Intron 9 of 14	ENST00000233575.7	NP_055563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX17	ENST00000233575.7	c.774+77T>C		intron_variant	Intron 9 of 14	1	NM_014748.4	ENSP00000233575.2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103458 AN: 151754 Hom.: 36997 Cov.: 30

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.612 AC: 717100 AN: 1172202 Hom.: 224005 AF XY: 0.614 AC XY: 361771 AN XY: 589544

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.744

Gnomad4 FIN exome AF: 0.621

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.682 AC: 103603 AN: 151872 Hom.: 37070 Cov.: 30 AF XY: 0.680 AC XY: 50448 AN XY: 74210

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.622

Alfa AF: 0.874 Hom.: 21163

Bravo AF: 0.691

Asia WGS AF: 0.677 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.73
DANN	Benign	0.15

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: rs4665972; hg19: chr2-27598097; COSMIC: COSV52007520; COSMIC: COSV52007520;