chr7-17821592-G-T

Variant names:

• chr7-17821592-G-T
• rs1453703804
• NM_015132.5:c.1762C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015132.5(SNX13):​c.1762C>A​(p.Arg588Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R588C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX13 NM_015132.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 3 publications found

Genes affected

SNX13 (HGNC:21335): (sorting nexin 13) This gene encodes a PHOX domain- and RGS domain-containing protein that belongs to the sorting nexin (SNX) family and the regulator of G protein signaling (RGS) family. The PHOX domain is a phosphoinositide binding domain, and the SNX family members are involved in intracellular trafficking. The RGS family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. The RGS domain of this protein interacts with G alpha(s), accelerates its GTP hydrolysis, and attenuates G alpha(s)-mediated signaling. Overexpression of this protein delayes lysosomal degradation of the epidermal growth factor receptor. Because of its bifunctional role, this protein may link heterotrimeric G protein signaling and vesicular trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015132.5. 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
	SNX13	NM_015132.5	MANE Select	c.1762C>A	p.Arg588Ser	missense	Exon 18 of 26	NP_055947.1	Q9Y5W8-2
	SNX13	NM_001350862.2		c.1795C>A	p.Arg599Ser	missense	Exon 18 of 26	NP_001337791.1	Q9Y5W8-1
	SNX13	NM_001350863.2		c.1522C>A	p.Arg508Ser	missense	Exon 18 of 26	NP_001337792.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX13	ENST00000428135.7	TSL:1 MANE Select	c.1762C>A	p.Arg588Ser	missense	Exon 18 of 26	ENSP00000398789.2	Q9Y5W8-2
	SNX13	ENST00000611725.4	TSL:1	c.1795C>A	p.Arg599Ser	missense	Exon 18 of 25	ENSP00000479044.1	A0A087WUZ7
	SNX13	ENST00000496855.1	TSL:1	n.106C>A		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
PhyloP100		3.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Polyphen		0.089	B
Vest4		0.71
MutPred		0.69		Loss of MoRF binding (P = 0.053)
MVP		0.56
MPC		0.46
ClinPred		0.50	D
GERP RS		5.8
gMVP		0.63
Mutation Taster		=31/69	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: rs1453703804; hg19: chr7-17861215;