8-100630379-G-C

Position:

• chr8-100630379-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152628.4(SNX31):​c.269C>G​(p.Pro90Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNX31 NM_152628.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX31	NM_152628.4	c.269C>G	p.Pro90Arg	missense_variant	4/14	ENST00000311812.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX31	ENST00000311812.7	c.269C>G	p.Pro90Arg	missense_variant	4/14	2	NM_152628.4	P1
SNX31	ENST00000520661.5	c.272C>G	p.Pro91Arg	missense_variant	4/5	3
SNX31	ENST00000520352.5	c.71C>G	p.Pro24Arg	missense_variant	3/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460648 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726604

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 0.00

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

Feb 16, 2023

The c.269C>G (p.P90R) alteration is located in exon 4 (coding exon 4) of the SNX31 gene. This alteration results from a C to G substitution at nucleotide position 269, causing the proline (P) at amino acid position 90 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.8	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0050	D;.;D
Polyphen		0.99	D;.;.
Vest4		0.77
MutPred		0.82		Gain of solvent accessibility (P = 0.0739);.;.;
MVP		0.50
MPC		0.12
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.35

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: chr8-101642607;