9-112838509-G-A

Position:

• chr9-112838509-G-A

Variant summary

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

The NM_001012994.2(SNX30):​c.826G>A​(p.Glu276Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

SNX30 (HGNC:23685): (sorting nexin family member 30) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in protein transport. [provided by Alliance of Genome Resources, Apr 2022]

SNX30 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX30	NM_001012994.2	c.826G>A	p.Glu276Lys	missense_variant	6/9	ENST00000374232.8	NP_001013012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX30	ENST00000374232.8	c.826G>A	p.Glu276Lys	missense_variant	6/9	5	NM_001012994.2	ENSP00000363349.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

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

Sep 08, 2024

The c.826G>A (p.E276K) alteration is located in exon 6 (coding exon 6) of the SNX30 gene. This alteration results from a G to A substitution at nucleotide position 826, causing the glutamic acid (E) at amino acid position 276 to be replaced by a lysine (K). 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	Pathogenic	0.97
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.78	P
Vest4		0.88
MutPred		0.50		Gain of ubiquitination at E276 (P = 0.0162);
MVP		0.22
MPC		1.1
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.69
gMVP		0.77

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: rs1362284406; hg19: chr9-115600789;