Genetic Variant SNX8:p.Gly461Ser (chr7-2255073-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013321.4(SNX8):c.1381G>A(p.Gly461Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,418,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SNX8
NM_013321.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

1 publications found

Variant links:

Genes affected

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

SNX8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042615205).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013321.4. 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
	SNX8	NM_013321.4	MANE Select	c.1381G>A	p.Gly461Ser	missense	Exon 11 of 11	NP_037453.1	Q9Y5X2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX8	ENST00000222990.8	TSL:1 MANE Select	c.1381G>A	p.Gly461Ser	missense	Exon 11 of 11	ENSP00000222990.3	Q9Y5X2
SNX8	ENST00000926983.1		c.1378G>A	p.Gly460Ser	missense	Exon 11 of 11	ENSP00000597042.1
SNX8	ENST00000878404.1		c.1372G>A	p.Gly458Ser	missense	Exon 11 of 11	ENSP00000548463.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

185576

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000776

AC:

AN:

1418360

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

701802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32436

American (AMR)

AF:

0.00

AC:

AN:

38668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

37230

South Asian (SAS)

AF:

0.00

AC:

AN:

80606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1090010

Other (OTH)

AF:

0.00

AC:

AN:

58736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

0.066

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.70

M_CAP

Benign

0.0093

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

PhyloP100

1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

0.39

REVEL

Benign

0.091

Sift

Benign

0.15

Sift4G

Benign

0.27

Polyphen

0.014

Vest4

0.020

MutPred

0.20

Gain of glycosylation at G461 (P = 0.002)

MVP

0.26

MPC

0.25

ClinPred

0.071

GERP RS

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.42

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over