chr7-17826070-C-T

Variant names:

• chr7-17826070-C-T
• rs778212225
• NM_015132.5:c.1657G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015132.5(SNX13):​c.1657G>A​(p.Val553Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,396,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: SNX13 NM_015132.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08484176).
• BS2: High AC in GnomAdExome4 at 37 AD gene.

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.1657G>A	p.Val553Ile	missense	Exon 17 of 26	NP_055947.1	Q9Y5W8-2
	SNX13	NM_001350862.2		c.1657G>A	p.Val553Ile	missense	Exon 17 of 26	NP_001337791.1	Q9Y5W8-1
	SNX13	NM_001350863.2		c.1417G>A	p.Val473Ile	missense	Exon 17 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.1657G>A	p.Val553Ile	missense	Exon 17 of 26	ENSP00000398789.2	Q9Y5W8-2
	SNX13	ENST00000611725.4	TSL:1	c.1657G>A	p.Val553Ile	missense	Exon 17 of 25	ENSP00000479044.1	A0A087WUZ7
	SNX13	ENST00000862559.1		c.1657G>A	p.Val553Ile	missense	Exon 17 of 26	ENSP00000532618.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000564 AC: 1 AN: 177320 AF XY: 0.00

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: 0.0000135

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000265 AC: 37 AN: 1396716 Hom.: 0 Cov.: 29 AF XY: 0.0000261 AC XY: 18 AN XY: 690048

African (AFR) AF: 0.00 AC: 0 AN: 31728

American (AMR) AF: 0.00 AC: 0 AN: 37888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24678

East Asian (EAS) AF: 0.00 AC: 0 AN: 36686

South Asian (SAS) AF: 0.00 AC: 0 AN: 76048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.0000334 AC: 36 AN: 1076706

Other (OTH) AF: 0.0000174 AC: 1 AN: 57474

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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	0.069
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.016
Sift	Benign	0.38	T
Sift4G	Benign	0.43	T
Polyphen		0.053	B
Vest4		0.15
MutPred		0.26		Gain of catalytic residue at S555 (P = 0.0769)
MVP		0.19
MPC		0.32
ClinPred		0.59	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.072
Mutation Taster		=94/6	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

dbSNP: rs778212225; hg19: chr7-17865693;