8-100596822-C-A

Position:

• chr8-100596822-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152628.4(SNX31):​c.795G>T​(p.Glu265Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX31 NM_152628.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.504

Genes affected

SNX31 (HGNC:28605): (sorting nexin 31) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in intracellular protein transport. Predicted to be located in cytoskeleton. Predicted to be part of protein-containing complex. Predicted to be active in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.20675424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX31	NM_152628.4	c.795G>T	p.Glu265Asp	missense_variant	10/14	ENST00000311812.7	NP_689841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX31	ENST00000311812.7	c.795G>T	p.Glu265Asp	missense_variant	10/14	2	NM_152628.4	ENSP00000312368	P1
SNX31	ENST00000428383.6	c.498G>T	p.Glu166Asp	missense_variant	7/11	1		ENSP00000405024

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.795G>T (p.E265D) alteration is located in exon 10 (coding exon 10) of the SNX31 gene. This alteration results from a G to T substitution at nucleotide position 795, causing the glutamic acid (E) at amino acid position 265 to be replaced by an aspartic acid (D). 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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0031	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.0080
Sift	Benign	0.17	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0010	B;B
Vest4		0.26
MutPred		0.30		Loss of helix (P = 0.1706);.;
MVP		0.20
MPC		0.072
ClinPred		0.068	T
GERP RS		1.8
Varity_R		0.056
gMVP		0.23

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

Other links and lift over

dbSNP: rs1384790109; hg19: chr8-101609050;