9-112751005-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001012994.2(SNX30):c.4G>T(p.Ala2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049868822).
• BP6: Variant 9-112751005-G-T is Benign according to our data. Variant chr9-112751005-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2534612.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX30	NM_001012994.2	c.4G>T	p.Ala2Ser	missense_variant	1/9	ENST00000374232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX30	ENST00000374232.8	c.4G>T	p.Ala2Ser	missense_variant	1/9	5	NM_001012994.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	16
Dann	Benign	0.95
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.96	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.039
Sift	Benign	0.82	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.12		Gain of glycosylation at A2 (P = 0.0031);
MVP		0.068
MPC		0.29
ClinPred		0.062	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.045
gMVP		0.21

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: chr9-115513285;