8-100573884-A-G

Position:

• chr8-100573884-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.1304T>C​(p.Ile435Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,424,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: SNX31 NM_152628.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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=0.108662784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX31	NM_152628.4	c.1304T>C	p.Ile435Thr	missense_variant	14/14	ENST00000311812.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX31	ENST00000311812.7	c.1304T>C	p.Ile435Thr	missense_variant	14/14	2	NM_152628.4	P1
SNX31	ENST00000428383.6	c.1007T>C	p.Ile336Thr	missense_variant	11/11	1
SNX31	ENST00000518342.1	c.128T>C	p.Ile43Thr	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1424112 Hom.: 0 Cov.: 27 AF XY: 0.00000282 AC XY: 2 AN XY: 708908

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: 0.00000549

Gnomad4 OTH exome AF: 0.00

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

May 06, 2024

The c.1304T>C (p.I435T) alteration is located in exon 14 (coding exon 14) of the SNX31 gene. This alteration results from a T to C substitution at nucleotide position 1304, causing the isoleucine (I) at amino acid position 435 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T;.
Eigen	Benign	0.063
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.86	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.12
Sift	Benign	0.042	D;D
Sift4G	Benign	0.091	T;T
Polyphen		0.60	P;P
Vest4		0.15
MutPred		0.26		Loss of catalytic residue at L440 (P = 0.012);.;
MVP		0.46
MPC		0.10
ClinPred		0.74	D
GERP RS		4.4
Varity_R		0.089
gMVP		0.16

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: rs1274516268; hg19: chr8-101586112;