Genetic Variant SNX13:p.Ala661Val (chr7-17814916-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015132.5(SNX13):c.1982C>T(p.Ala661Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNX13
NM_015132.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

Publications

0 publications found

Variant links:

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]

SNX13 links:

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ACMG classification

Classification was made for transcript

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=0.3952111).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX13	NM_015132.5	MANE Select	c.1982C>T	p.Ala661Val	missense	Exon 20 of 26	NP_055947.1	Q9Y5W8-2
SNX13	NM_001350862.2		c.2015C>T	p.Ala672Val	missense	Exon 20 of 26	NP_001337791.1	Q9Y5W8-1
SNX13	NM_001350863.2		c.1742C>T	p.Ala581Val	missense	Exon 20 of 26	NP_001337792.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX13	ENST00000428135.7	TSL:1 MANE Select	c.1982C>T	p.Ala661Val	missense	Exon 20 of 26	ENSP00000398789.2	Q9Y5W8-2
SNX13	ENST00000611725.4	TSL:1	c.2015C>T	p.Ala672Val	missense	Exon 20 of 25	ENSP00000479044.1	A0A087WUZ7
SNX13	ENST00000496855.1	TSL:1	n.326C>T		non_coding_transcript_exon	Exon 3 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1354658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

669450

African (AFR)

AF:

0.00

AC:

AN:

27200

American (AMR)

AF:

0.00

AC:

AN:

22482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23494

East Asian (EAS)

AF:

0.00

AC:

AN:

32586

South Asian (SAS)

AF:

0.00

AC:

AN:

67464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069552

Other (OTH)

AF:

0.00

AC:

AN:

56046

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.016

MetaRNN

Benign

0.40

MetaSVM

Benign

-1.1

PhyloP100

7.7

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.2

REVEL

Benign

0.13

Sift

Benign

0.13

Sift4G

Benign

0.31

Polyphen

0.13

Vest4

0.58

MutPred

0.44

Loss of helix (P = 0.0376)

MVP

0.16

MPC

0.44

ClinPred

0.89

GERP RS

5.8

gMVP

0.45

Mutation Taster

=51/49

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over