Genetic Variant STOML1:p.Gly342Arg (chr15-73984110-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004809.5(STOML1):c.1024G>A(p.Gly342Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,613,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

STOML1
NM_004809.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

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]

STOML1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122133166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOML1	NM_004809.5 link	c.1024G>A	p.Gly342Arg	missense_variant	Exon 7 of 7	ENST00000541638.6	NP_004800.2	Q9UBI4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOML1	ENST00000541638.6 link	c.1024G>A	p.Gly342Arg	missense_variant	Exon 7 of 7	1	NM_004809.5	ENSP00000442478.2		Q9UBI4-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000300

AC:

AN:

250236

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000496

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000369

AC:

539

AN:

1460764

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

262

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000438

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000164

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000349

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1024G>A (p.G342R) alteration is located in exon 7 (coding exon 7) of the STOML1 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the glycine (G) at amino acid position 342 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;.;.;T;.

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.5

M;.;.;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.9

.;D;D;.;D;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.0040

.;D;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.96

D;.;D;.;.;.

Vest4

0.22

MutPred

0.76

Gain of solvent accessibility (P = 0.0456);.;.;.;.;.;

MVP

0.23

MPC

1.2

ClinPred

0.58

GERP RS

4.4

Varity_R

0.33

gMVP

0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over