15-73988693-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004809.5(STOML1):​c.500G>T​(p.Arg167Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R167H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.70
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

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>T	p.Arg167Leu	missense	Exon 4 of 7	NP_004800.2
	STOML1	NM_001256672.2		c.500G>T	p.Arg167Leu	missense	Exon 4 of 7	NP_001243601.1	Q9UBI4-3
	STOML1	NM_001324230.2		c.374G>T	p.Arg125Leu	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>T	p.Arg167Leu	missense	Exon 4 of 7	ENSP00000442478.2	Q9UBI4-1
	STOML1	ENST00000316911.10	TSL:1	c.350G>T	p.Arg117Leu	missense	Exon 3 of 6	ENSP00000319384.6	Q9UBI4-2
	STOML1	ENST00000564777.5	TSL:1	c.350G>T	p.Arg117Leu	missense	Exon 3 of 6	ENSP00000456343.1	Q9UBI4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 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: 0.0000116 AC: 1 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: 8.99e-7 AC: 1 AN: 1112012

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Benign	0.98	L
PhyloP100		6.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.57		Loss of MoRF binding (P = 0.0039)
MVP		0.82
MPC		0.74
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.79
gMVP		0.80
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;