chr8-100588925-G-A

Position:

• chr8-100588925-G-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.1033C>T​(p.Leu345Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SNX31 NM_152628.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

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=0.25207728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX31	NM_152628.4	c.1033C>T	p.Leu345Phe	missense_variant	11/14	ENST00000311812.7	NP_689841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX31	ENST00000311812.7	c.1033C>T	p.Leu345Phe	missense_variant	11/14	2	NM_152628.4	ENSP00000312368.2
SNX31	ENST00000428383.6	c.736C>T	p.Leu246Phe	missense_variant	8/11	1		ENSP00000405024.2
SNX31	ENST00000519521.1	n.123C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

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

Nov 25, 2024

The c.1033C>T (p.L345F) alteration is located in exon 11 (coding exon 11) of the SNX31 gene. This alteration results from a C to T substitution at nucleotide position 1033, causing the leucine (L) at amino acid position 345 to be replaced by a phenylalanine (F). 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	0.21
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.16
Sift	Benign	0.055	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;B
Vest4		0.32
MutPred		0.53		Gain of loop (P = 0.0312);.;
MVP		0.44
MPC		0.11
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.28

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: rs1814308265; hg19: chr8-101601153;