Variant 1-98685060-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015976.5(SNX7):c.356T>C(p.Ile119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000069 in 1,477,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041210204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX7	NM_015976.5 linkuse as main transcript	c.356T>C	p.Ile119Thr	missense_variant	2/9	ENST00000306121.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX7	ENST00000306121.8 linkuse as main transcript	c.356T>C	p.Ile119Thr	missense_variant	2/9	1	NM_015976.5	P1	Q9UNH6-3
SNX7	ENST00000528824.1 linkuse as main transcript	c.*176T>C		3_prime_UTR_variant, NMD_transcript_variant	3/9	1
SNX7	ENST00000529992.5 linkuse as main transcript	c.356T>C	p.Ile119Thr	missense_variant	2/8	2
SNX7	ENST00000454199.1 linkuse as main transcript	c.164T>C	p.Ile55Thr	missense_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000708

AC:

AN:

197682

Hom.:

AF XY:

0.0000928

AC XY:

AN XY:

107750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000494

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000498

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000717

AC:

AN:

1325148

Hom.:

Cov.:

AF XY:

0.0000724

AC XY:

AN XY:

648810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000337

Gnomad4 AMR exome

AF:

0.0000948

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000849

Gnomad4 OTH exome

AF:

0.0000372

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000856

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000742

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

May 23, 2023

The c.356T>C (p.I119T) alteration is located in exon 2 (coding exon 2) of the SNX7 gene. This alteration results from a T to C substitution at nucleotide position 356, causing the isoleucine (I) at amino acid position 119 to be replaced by a threonine (T). 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

-0.32

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.23

DEOGEN2

Benign

0.0086

T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.085

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.027

B;B;.

Vest4

0.28

MutPred

0.42

Loss of stability (P = 0.0141);Loss of stability (P = 0.0141);.;

MVP

0.061

MPC

0.12

ClinPred

0.019

GERP RS

3.1

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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