Genetic Variant STOML2:p.Arg51Gln (chr9-35102717-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_013442.3(STOML2):c.152G>A(p.Arg51Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,960 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STOML2
NM_013442.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45

Variant links:

Genes affected

STOML2 (HGNC:14559): (stomatin like 2) Enables GTPase binding activity and cardiolipin binding activity. Involved in several processes, including inorganic cation transmembrane transport; positive regulation of cardiolipin metabolic process; and positive regulation of mitochondrial DNA replication. Located in membrane raft; mitochondrial inner membrane; and mitochondrial intermembrane space. Is extrinsic component of plasma membrane. Colocalizes with several cellular components, including COP9 signalosome; T cell receptor complex; and immunological synapse. [provided by Alliance of Genome Resources, Apr 2022]

STOML2 links:

PIGO-AS1 (HGNC:55692): (PIGO antisense RNA 1)

PIGO-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOML2	NM_013442.3 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 10	ENST00000356493.10	NP_038470.1	Q9UJZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STOML2	ENST00000356493.10 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 10	1	NM_013442.3	ENSP00000348886.5	Q9UJZ1-1
STOML2	ENST00000452248.6 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 9	2		ENSP00000395743.2	Q9UJZ1-2
STOML2	ENST00000619795.4 link	c.45+333G>A		intron_variant	Intron 1 of 8	3		ENSP00000481672.1	A0A087WYB4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251232

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460960

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152G>A (p.R51Q) alteration is located in exon 2 (coding exon 2) of the STOML2 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the arginine (R) at amino acid position 51 to be replaced by a glutamine (Q). 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

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.55

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.74

.;D

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.9

D;D

REVEL

Pathogenic

0.94

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.95

MutPred

0.87

Loss of MoRF binding (P = 0.0877);Loss of MoRF binding (P = 0.0877);

MVP

0.94

MPC

1.4

ClinPred

1.0

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.86

gMVP

0.89

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

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