rs1245845733

Variant names:

• chr15-73985323-C-A
• rs1245845733
• NM_004809.5:c.785G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-73985323-C-A
• chr15-73985323-C-T

Variant summary

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

The NM_004809.5(STOML1):​c.785G>T​(p.Gly262Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000654 in 1,529,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

Genes affected

STOML1 (HGNC:14560): (stomatin like 1) Predicted to enable ion channel inhibitor activity. Predicted to be involved in lipid transport. Predicted to act upstream of or within SMAD protein signal transduction; cellular response to leukemia inhibitory factor; and negative regulation of acid-sensing ion channel activity. Predicted to be located in cytoplasmic vesicle. Predicted to be active in plasma membrane. [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=0.11191192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004809.5. 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
	STOML1	NM_004809.5	MANE Select	c.785G>T	p.Gly262Val	missense	Exon 5 of 7	NP_004800.2
	STOML1	NM_001256672.2		c.785G>T	p.Gly262Val	missense	Exon 5 of 7	NP_001243601.1	Q9UBI4-3
	STOML1	NM_001324230.2		c.659G>T	p.Gly220Val	missense	Exon 6 of 8	NP_001311159.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOML1	ENST00000541638.6	TSL:1 MANE Select	c.785G>T	p.Gly262Val	missense	Exon 5 of 7	ENSP00000442478.2	Q9UBI4-1
	STOML1	ENST00000316911.10	TSL:1	c.635G>T	p.Gly212Val	missense	Exon 4 of 6	ENSP00000319384.6	Q9UBI4-2
	STOML1	ENST00000564777.5	TSL:1	c.635G>T	p.Gly212Val	missense	Exon 4 of 6	ENSP00000456343.1	Q9UBI4-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 177966 AF XY: 0.00

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 AF: 0.00000653 AC: 9 AN: 1377526 Hom.: 0 Cov.: 30 AF XY: 0.00000736 AC XY: 5 AN XY: 679010

African (AFR) AF: 0.00 AC: 0 AN: 29888

American (AMR) AF: 0.00 AC: 0 AN: 28182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21034

East Asian (EAS) AF: 0.00 AC: 0 AN: 37908

South Asian (SAS) AF: 0.00 AC: 0 AN: 71852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.00000743 AC: 8 AN: 1076896

Other (OTH) AF: 0.0000177 AC: 1 AN: 56594

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.072
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	13
DANN	Benign	0.65
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	0.81	L
PhyloP100		2.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Benign	0.040	D
Sift4G	Benign	0.069	T
Polyphen		0.50	P
Vest4		0.25
MutPred		0.16		Loss of glycosylation at P261 (P = 0.094)
MVP		0.41
MPC		0.42
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.053
gMVP		0.29
Mutation Taster		=96/4	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: rs1245845733; hg19: chr15-74277664;