15-73985368-A-G

Variant names:

• chr15-73985368-A-G
• rs768433983
• NM_004809.5:c.740T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004809.5(STOML1):​c.740T>C​(p.Leu247Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,559,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37394845).

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.740T>C	p.Leu247Pro	missense	Exon 5 of 7	NP_004800.2
	STOML1	NM_001256672.2		c.740T>C	p.Leu247Pro	missense	Exon 5 of 7	NP_001243601.1	Q9UBI4-3
	STOML1	NM_001324230.2		c.614T>C	p.Leu205Pro	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.740T>C	p.Leu247Pro	missense	Exon 5 of 7	ENSP00000442478.2	Q9UBI4-1
	STOML1	ENST00000316911.10	TSL:1	c.590T>C	p.Leu197Pro	missense	Exon 4 of 6	ENSP00000319384.6	Q9UBI4-2
	STOML1	ENST00000564777.5	TSL:1	c.590T>C	p.Leu197Pro	missense	Exon 4 of 6	ENSP00000456343.1	Q9UBI4-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.0000393 AC: 8 AN: 203744 AF XY: 0.0000534

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000455

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000718

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000126 AC: 177 AN: 1407740 Hom.: 0 Cov.: 30 AF XY: 0.000123 AC XY: 86 AN XY: 698028

African (AFR) AF: 0.00 AC: 0 AN: 30280

American (AMR) AF: 0.0000320 AC: 1 AN: 31274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23738

East Asian (EAS) AF: 0.00 AC: 0 AN: 37396

South Asian (SAS) AF: 0.00 AC: 0 AN: 78442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.000160 AC: 174 AN: 1090910

Other (OTH) AF: 0.0000345 AC: 2 AN: 57918

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74350

African (AFR) AF: 0.0000482 AC: 2 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15288

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: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000569 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00000824 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	0.28
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.37	T
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Benign	1.0	L
PhyloP100		4.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.35	N
REVEL	Pathogenic	0.72
Sift	Benign	0.045	D
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.51		Loss of stability (P = 0.0098)
MVP		0.85
MPC		0.62
ClinPred		0.32	T
GERP RS		5.2
Varity_R		0.68
gMVP		0.84
Mutation Taster		=24/76	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: rs768433983; hg19: chr15-74277709;