rs774464130

Variant names:

• chr15-73988693-C-T
• rs774464130
• NM_004809.5:c.500G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-73988693-C-T
• chr15-73988693-C-A
• chr15-73988693-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004809.5(STOML1):​c.500G>A​(p.Arg167His) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

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.500G>A	p.Arg167His	missense	Exon 4 of 7	NP_004800.2
	STOML1	NM_001256672.2		c.500G>A	p.Arg167His	missense	Exon 4 of 7	NP_001243601.1	Q9UBI4-3
	STOML1	NM_001324230.2		c.374G>A	p.Arg125His	missense	Exon 5 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.500G>A	p.Arg167His	missense	Exon 4 of 7	ENSP00000442478.2	Q9UBI4-1
	STOML1	ENST00000316911.10	TSL:1	c.350G>A	p.Arg117His	missense	Exon 3 of 6	ENSP00000319384.6	Q9UBI4-2
	STOML1	ENST00000564777.5	TSL:1	c.350G>A	p.Arg117His	missense	Exon 3 of 6	ENSP00000456343.1	Q9UBI4-4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251478 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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: 0.0000294 AC: 2 AN: 68038

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.58		Loss of MoRF binding (P = 0.0064)
MVP		0.90
MPC		0.81
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.73
gMVP		0.70
Mutation Taster		=49/51	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: rs774464130; hg19: chr15-74281034; COSMIC: COSV57550989; COSMIC: COSV57550989;