chr2-27374385-C-G

Variant names:

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

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>G​(p.Ser188Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SNX17 NM_014748.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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, 0.879

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>G	p.Ser188Cys	missense	Exon 7 of 15	NP_055563.1	Q15036-1
	SNX17	NM_001267059.2		c.527C>G	p.Ser176Cys	missense	Exon 7 of 15	NP_001253988.1	B4DTB8
	SNX17	NM_001267061.2		c.503C>G	p.Ser168Cys	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>G	p.Ser188Cys	missense	Exon 7 of 15	ENSP00000233575.2	Q15036-1
	SNX17	ENST00000440760.5	TSL:1	n.*408C>G		non_coding_transcript_exon	Exon 6 of 14	ENSP00000399727.1	F8WFA0
	SNX17	ENST00000453453.1	TSL:1	n.*160C>G		non_coding_transcript_exon	Exon 5 of 12	ENSP00000401922.1	F8WEG6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251440 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461840 Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 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: 0.0000414 AC: 46 AN: 1111970

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.67		Gain of helix (P = 0.0199)
MVP		0.79
MPC		0.75
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.73
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;