NM_004809.5:c.910G>A

Variant names:

• chr15-73984752-C-T
• NM_004809.5:c.910G>A

Variant summary

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

The NM_004809.5(STOML1):​c.910G>A​(p.Glu304Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E304E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.910G>A	p.Glu304Lys	missense	Exon 6 of 7	NP_004800.2
	STOML1	NM_001256672.2		c.907G>A	p.Glu303Lys	missense	Exon 6 of 7	NP_001243601.1	Q9UBI4-3
	STOML1	NM_001324230.2		c.784G>A	p.Glu262Lys	missense	Exon 7 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.910G>A	p.Glu304Lys	missense	Exon 6 of 7	ENSP00000442478.2	Q9UBI4-1
	STOML1	ENST00000316911.10	TSL:1	c.760G>A	p.Glu254Lys	missense	Exon 5 of 6	ENSP00000319384.6	Q9UBI4-2
	STOML1	ENST00000564777.5	TSL:1	c.757G>A	p.Glu253Lys	missense	Exon 5 of 6	ENSP00000456343.1	Q9UBI4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.014	D
Polyphen		0.94	P
Vest4		0.73
MutPred		0.50		Gain of ubiquitination at E304 (P = 0.0185)
MVP		0.12
MPC		0.70
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.21
gMVP		0.51

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

hg19: chr15-74277093;