NM_001012994.2:c.115C>G

Variant names:

• chr9-112751116-C-G
• rs754639852
• NM_001012994.2:c.115C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001012994.2(SNX30):​c.115C>G​(p.Pro39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,520,654 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11980656).

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.115C>G	p.Pro39Ala	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.115C>G	p.Pro39Ala	missense	Exon 1 of 9	ENSP00000363349.3	Q5VWJ9
	SNX30	ENST00000870319.1		c.115C>G	p.Pro39Ala	missense	Exon 1 of 8	ENSP00000540378.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD2 exomes AF: 0.0000233 AC: 3 AN: 128526 AF XY: 0.0000277

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 19 AN: 1368544 Hom.: 0 Cov.: 31 AF XY: 0.0000148 AC XY: 10 AN XY: 676464

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000340 AC: 1 AN: 29412

American (AMR) AF: 0.0000613 AC: 2 AN: 32644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24026

East Asian (EAS) AF: 0.00 AC: 0 AN: 33598

South Asian (SAS) AF: 0.00 AC: 0 AN: 76000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35706

Middle Eastern (MID) AF: 0.000204 AC: 1 AN: 4900

European-Non Finnish (NFE) AF: 0.0000130 AC: 14 AN: 1074958

Other (OTH) AF: 0.0000175 AC: 1 AN: 57300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000253707), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000901 AC: 1

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	0.055
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.36	T
Polyphen		0.98	D
Vest4		0.18
MutPred		0.11		Loss of phosphorylation at T38 (P = 0.088)
MVP		0.14
MPC		0.31
ClinPred		0.24	T
GERP RS		4.5
PromoterAI		0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.40
Mutation Taster		=86/14	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: rs754639852; hg19: chr9-115513396;