9-112751091-G-C

Variant names:

• chr9-112751091-G-C
• rs1220311806
• NM_001012994.2:c.90G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012994.2(SNX30):​c.90G>C​(p.Glu30Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000733 in 1,363,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 7.3e-7 (0 hom.)
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1140939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012994.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX30	NM_001012994.2	MANE Select	c.90G>C	p.Glu30Asp	missense	Exon 1 of 9	NP_001013012.1	Q5VWJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX30	ENST00000374232.8	TSL:5 MANE Select	c.90G>C	p.Glu30Asp	missense	Exon 1 of 9	ENSP00000363349.3	Q5VWJ9
	SNX30	ENST00000870319.1		c.90G>C	p.Glu30Asp	missense	Exon 1 of 8	ENSP00000540378.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1363524 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 673476

African (AFR) AF: 0.00 AC: 0 AN: 29240

American (AMR) AF: 0.00 AC: 0 AN: 32262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24190

East Asian (EAS) AF: 0.00 AC: 0 AN: 33218

South Asian (SAS) AF: 0.00 AC: 0 AN: 76248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4594

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071494

Other (OTH) AF: 0.00 AC: 0 AN: 57072

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0013
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.057
Sift	Uncertain	0.020	D
Sift4G	Benign	0.37	T
Polyphen		0.25	B
Vest4		0.22
MutPred		0.10		Gain of glycosylation at S27 (P = 0.1411)
MVP		0.10
MPC		0.29
ClinPred		0.56	D
GERP RS		4.3
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.16
gMVP		0.28
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1220311806; hg19: chr9-115513371;