NM_001012994.2:c.121C>T

Variant names:

• chr9-112751122-C-T
• rs780735230
• NM_001012994.2:c.121C>T

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.121C>T​(p.Pro41Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNX30 NM_001012994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• 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=0.14509472).

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.121C>T	p.Pro41Ser	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.121C>T	p.Pro41Ser	missense	Exon 1 of 9	ENSP00000363349.3	Q5VWJ9
	SNX30	ENST00000870319.1		c.121C>T	p.Pro41Ser	missense	Exon 1 of 8	ENSP00000540378.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 2 AN: 125446 AF XY: 0.0000285

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000367 AC: 5 AN: 1362938 Hom.: 1 Cov.: 30 AF XY: 0.00000743 AC XY: 5 AN XY: 673118

African (AFR) AF: 0.00 AC: 0 AN: 29318

American (AMR) AF: 0.00 AC: 0 AN: 32208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23620

East Asian (EAS) AF: 0.00 AC: 0 AN: 33476

South Asian (SAS) AF: 0.0000534 AC: 4 AN: 74856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4800

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072088

Other (OTH) AF: 0.00 AC: 0 AN: 57034

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000180 AC: 2

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	0.084
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.15
Sift	Benign	0.27	T
Sift4G	Benign	0.40	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.097		Gain of phosphorylation at P41 (P = 0.028)
MVP		0.093
MPC		0.34
ClinPred		0.70	D
GERP RS		4.6
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.14
gMVP		0.48
Mutation Taster		=47/53	disease causing

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: rs780735230; hg19: chr9-115513402;