Variant chr1-98661786-G-A 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.55G>A(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,243,718 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G19C) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

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:

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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=0.27473778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX7	NM_015976.5 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	1/9	ENST00000306121.8	NP_057060.2	Q9UNH6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNX7	ENST00000306121.8 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	1/9	1	NM_015976.5	ENSP00000304429.3	Q9UNH6-3
SNX7	ENST00000529992.5 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	1/8	2		ENSP00000434731.1	E9PNL2
SNX7	ENST00000473868.5 linkuse as main transcript	n.-24G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

13002

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

6142

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000364

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000660

AC:

AN:

1091610

Hom.:

Cov.:

AF XY:

0.0000640

AC XY:

AN XY:

515416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000205

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000707

Gnomad4 OTH exome

AF:

0.0000459

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

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

Sep 17, 2021

The c.55G>A (p.G19S) alteration is located in exon 1 (coding exon 1) of the SNX7 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glycine (G) at amino acid position 19 to be replaced by a serine (S). 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

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;T

Polyphen

1.0

D;D

Vest4

0.31

MutPred

0.20

Gain of phosphorylation at G19 (P = 0.0092);Gain of phosphorylation at G19 (P = 0.0092);

MVP

0.67

MPC

0.47

ClinPred

0.30

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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