Genetic Variant STOML2:p.Arg34Gln (chr9-35102768-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013442.3(STOML2):c.101G>A(p.Arg34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,613,964 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R34G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

STOML2
NM_013442.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Publications

3 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26090965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013442.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOML2	NM_013442.3	MANE Select	c.101G>A	p.Arg34Gln	missense	Exon 2 of 10	NP_038470.1	Q9UJZ1-1
STOML2	NM_001287031.2		c.101G>A	p.Arg34Gln	missense	Exon 2 of 9	NP_001273960.1	Q9UJZ1-2
STOML2	NM_001287032.1		c.-53G>A		5_prime_UTR	Exon 2 of 10	NP_001273961.1	Q9UJZ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOML2	ENST00000356493.10	TSL:1 MANE Select	c.101G>A	p.Arg34Gln	missense	Exon 2 of 10	ENSP00000348886.5	Q9UJZ1-1
STOML2	ENST00000940083.1		c.101G>A	p.Arg34Gln	missense	Exon 2 of 10	ENSP00000610142.1
STOML2	ENST00000940081.1		c.101G>A	p.Arg34Gln	missense	Exon 2 of 10	ENSP00000610140.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000598

AC:

AN:

250918

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1112002

Other (OTH)

AF:

0.0000497

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000105

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Benign

-0.034

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.26

MetaSVM

Uncertain

0.44

MutationAssessor

Benign

1.2

PhyloP100

5.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.19

REVEL

Uncertain

0.38

Sift

Benign

0.28

Sift4G

Benign

0.29

Polyphen

0.31

Vest4

0.32

MVP

0.68

MPC

1.1

ClinPred

0.29

GERP RS

5.4

PromoterAI

0.0035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.56

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over