Variant 1-98684945-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015976.5(SNX7):c.241A>G(p.Met81Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,598,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32

Variant links:

Genes affected

SNX7 (HGNC:14971): (sorting nexin 7) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region like some family members, and its exact function is unknown. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Jun 2010]

SNX7 links:

SNX7 (HGNC:):

SNX7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38256642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX7	NM_015976.5 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	2/9	ENST00000306121.8	NP_057060.2	Q9UNH6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX7	ENST00000306121.8 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	2/9	1	NM_015976.5	ENSP00000304429.3		Q9UNH6-3

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248134

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134100

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1446456

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

718368

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000997

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.241A>G (p.M81V) alteration is located in exon 2 (coding exon 2) of the SNX7 gene. This alteration results from a A to G substitution at nucleotide position 241, causing the methionine (M) at amino acid position 81 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.039

D;T;T

Polyphen

0.85

P;P;.

Vest4

0.66

MVP

0.77

MPC

0.43

ClinPred

0.80

GERP RS

5.4

gMVP

0.53

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