2-27374385-C-T

Variant names:

• chr2-27374385-C-T
• rs749634634
• NM_014748.4:c.563C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014748.4(SNX17):​c.563C>T​(p.Ser188Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S188C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNX17 NM_014748.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014748.4. 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
	SNX17	NM_014748.4	MANE Select	c.563C>T	p.Ser188Phe	missense	Exon 7 of 15	NP_055563.1	Q15036-1
	SNX17	NM_001267059.2		c.527C>T	p.Ser176Phe	missense	Exon 7 of 15	NP_001253988.1	B4DTB8
	SNX17	NM_001267061.2		c.503C>T	p.Ser168Phe	missense	Exon 7 of 15	NP_001253990.1	B4DQ37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX17	ENST00000233575.7	TSL:1 MANE Select	c.563C>T	p.Ser188Phe	missense	Exon 7 of 15	ENSP00000233575.2	Q15036-1
	SNX17	ENST00000440760.5	TSL:1	n.*408C>T		non_coding_transcript_exon	Exon 6 of 14	ENSP00000399727.1	F8WFA0
	SNX17	ENST00000453453.1	TSL:1	n.*160C>T		non_coding_transcript_exon	Exon 5 of 12	ENSP00000401922.1	F8WEG6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.063	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.69		Gain of helix (P = 0.0325)
MVP		0.95
MPC		0.79
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.78
gMVP		0.82
Mutation Taster		=16/84	disease causing

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: rs749634634; hg19: chr2-27597252; COSMIC: COSV52008144; COSMIC: COSV52008144;