8-100596695-T-G

Position:

• chr8-100596695-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152628.4(SNX31):​c.922A>C​(p.Thr308Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 3.59

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3599903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX31	NM_152628.4	c.922A>C	p.Thr308Pro	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.922A>C	p.Thr308Pro	missense_variant	10/14	2	NM_152628.4	ENSP00000312368	P1
SNX31	ENST00000428383.6	c.625A>C	p.Thr209Pro	missense_variant	7/11	1		ENSP00000405024
SNX31	ENST00000519521.1	n.12A>C		non_coding_transcript_exon_variant	1/4	3

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

Mar 23, 2022

The c.922A>C (p.T308P) alteration is located in exon 10 (coding exon 10) of the SNX31 gene. This alteration results from a A to C substitution at nucleotide position 922, causing the threonine (T) at amino acid position 308 to be replaced by a proline (P). 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	0.094
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0060	T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.058
Sift	Benign	0.12	T;T
Sift4G	Benign	0.070	T;D
Polyphen		0.99	D;D
Vest4		0.51
MutPred		0.37		Loss of helix (P = 0.0237);.;
MVP		0.40
MPC		0.44
ClinPred		0.81	D
GERP RS		3.4
Varity_R		0.42
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-101608923;