8-100596742-A-G

Position:

• chr8-100596742-A-G

Variant summary

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

The NM_152628.4(SNX31):​c.875T>C​(p.Val292Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SNX31 NM_152628.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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=0.14982668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX31	NM_152628.4	c.875T>C	p.Val292Ala	missense_variant	10/14	ENST00000311812.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX31	ENST00000311812.7	c.875T>C	p.Val292Ala	missense_variant	10/14	2	NM_152628.4	P1
SNX31	ENST00000428383.6	c.578T>C	p.Val193Ala	missense_variant	7/11	1
SNX31	ENST00000519521.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461878 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727240

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 08, 2023

The c.875T>C (p.V292A) alteration is located in exon 10 (coding exon 10) of the SNX31 gene. This alteration results from a T to C substitution at nucleotide position 875, causing the valine (V) at amino acid position 292 to be replaced by an alanine (A). 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	0.22
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.74
DEOGEN2	Benign	0.0056	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.083
Sift	Benign	0.79	T;T
Sift4G	Benign	0.16	T;D
Polyphen		0.68	P;B
Vest4		0.090
MutPred		0.47		Gain of disorder (P = 0.0425);.;
MVP		0.10
MPC		0.11
ClinPred		0.21	T
GERP RS		3.3
Varity_R		0.070
gMVP		0.39

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: rs989200148; hg19: chr8-101608970; COSMIC: COSV61262813; COSMIC: COSV61262813;