Variant 6-157901963-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016224.5(SNX9):c.538G>A(p.Asp180Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,613,460 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 7 hom., cov: 31)

Exomes 𝑓: 0.011 ( 127 hom. )

Consequence

SNX9
NM_016224.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.72

Variant links:

Genes affected

SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

SNX9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004186243).

BP6

Variant 6-157901963-G-A is Benign according to our data. Variant chr6-157901963-G-A is described in ClinVar as [Benign]. Clinvar id is 790318.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX9	NM_016224.5 linkuse as main transcript	c.538G>A	p.Asp180Asn	missense_variant	6/18	ENST00000392185.8	NP_057308.1
SNX9	XM_011535886.4 linkuse as main transcript	c.256G>A	p.Asp86Asn	missense_variant	3/15		XP_011534188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX9	ENST00000392185.8 linkuse as main transcript	c.538G>A	p.Asp180Asn	missense_variant	6/18	1	NM_016224.5	ENSP00000376024	P1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1131

AN:

151580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00565

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00708

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00962

GnomAD3 exomes

AF:

0.00830

AC:

2085

AN:

251310

Hom.:

AF XY:

0.00896

AC XY:

1217

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00370

Gnomad AMR exome

AF:

0.00544

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00928

Gnomad FIN exome

AF:

0.00568

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.0112

AC:

16343

AN:

1461770

Hom.:

127

Cov.:

AF XY:

0.0112

AC XY:

8129

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.00628

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00860

Gnomad4 FIN exome

AF:

0.00537

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00916

GnomAD4 genome

AF:

0.00745

AC:

1130

AN:

151690

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

538

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.00373

Gnomad4 AMR

AF:

0.00565

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00688

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00952

Alfa

AF:

0.00937

Hom.:

Bravo

AF:

0.00699

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00872

AC:

1059

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Benign

-0.20

Eigen_PC

Benign

0.00080

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.33

REVEL

Benign

0.13

Sift

Benign

0.13

Sift4G

Benign

0.39

Polyphen

0.0020

Vest4

0.24

MVP

0.58

MPC

0.10

ClinPred

0.019

GERP RS

5.4

Varity_R

0.15

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over