Genetic Variant NM_015976.5:c.64G>C (chr1-98661795-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015976.5(SNX7):c.64G>C(p.Gly22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,244,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10262352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX7	NM_015976.5 link	c.64G>C	p.Gly22Arg	missense_variant	Exon 1 of 9	ENST00000306121.8	NP_057060.2	Q9UNH6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNX7	ENST00000306121.8 link	c.64G>C	p.Gly22Arg	missense_variant	Exon 1 of 9	1	NM_015976.5	ENSP00000304429.3	Q9UNH6-3
SNX7	ENST00000529992.5 link	c.64G>C	p.Gly22Arg	missense_variant	Exon 1 of 8	2		ENSP00000434731.1	E9PNL2
SNX7	ENST00000528824.1 link	n.-126G>C		upstream_gene_variant		1		ENSP00000435172.1	E9PLE1
SNX7	ENST00000473868.5 link	n.-15G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152026

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1092382

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

515734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000120

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:

0.0000131

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.65

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.091

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.089

T;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.23

Gain of methylation at G22 (P = 0.0722);Gain of methylation at G22 (P = 0.0722);

MVP

0.36

MPC

0.42

ClinPred

0.28

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over