NM_014748.4:c.273G>T

Variant names:

• chr2-27373263-G-T
• NM_014748.4:c.273G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014748.4(SNX17):​c.273G>T​(p.Leu91Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX17 NM_014748.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3117774).

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.273G>T	p.Leu91Phe	missense	Exon 4 of 15	NP_055563.1	Q15036-1
	SNX17	NM_001267059.2		c.237G>T	p.Leu79Phe	missense	Exon 4 of 15	NP_001253988.1	B4DTB8
	SNX17	NM_001267061.2		c.213G>T	p.Leu71Phe	missense	Exon 4 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.273G>T	p.Leu91Phe	missense	Exon 4 of 15	ENSP00000233575.2	Q15036-1
	SNX17	ENST00000440760.5	TSL:1	n.*118G>T		non_coding_transcript_exon	Exon 3 of 14	ENSP00000399727.1	F8WFA0
	SNX17	ENST00000453453.1	TSL:1	n.80G>T		non_coding_transcript_exon	Exon 2 of 12	ENSP00000401922.1	F8WEG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.00041
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.092
Sift	Benign	0.069	T
Sift4G	Uncertain	0.054	T
Polyphen		0.031	B
Vest4		0.56
MutPred		0.41		Loss of relative solvent accessibility (P = 0.114)
MVP		0.46
MPC		0.23
ClinPred		0.34	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.19
Mutation Taster		=251/49	polymorphism

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

hg19: chr2-27596130;