9-112836355-C-T

Variant summary

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

The NM_001012994.2(SNX30):c.760C>T(p.Leu254Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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]

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=0.39479497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX30	NM_001012994.2	c.760C>T	p.Leu254Phe	missense_variant	5/9	ENST00000374232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX30	ENST00000374232.8	c.760C>T	p.Leu254Phe	missense_variant	5/9	5	NM_001012994.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457628 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724096

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 07, 2023

The c.760C>T (p.L254F) alteration is located in exon 5 (coding exon 5) of the SNX30 gene. This alteration results from a C to T substitution at nucleotide position 760, causing the leucine (L) at amino acid position 254 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	0.15
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.15
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.046	D
Polyphen		0.98	D
Vest4		0.51
MutPred		0.47		Gain of catalytic residue at L254 (P = 0.0281);
MVP		0.093
MPC		0.70
ClinPred		0.88	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-115598635;