9-35100997-C-T

Variant summary

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

The NM_013442.3(STOML2):​c.739G>A​(p.Val247Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94
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]
PIGO-AS1 (HGNC:55692): (PIGO antisense RNA 1)

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=0.074638665).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STOML2NM_013442.3 linkc.739G>A p.Val247Ile missense_variant Exon 8 of 10 ENST00000356493.10 NP_038470.1 Q9UJZ1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STOML2ENST00000356493.10 linkc.739G>A p.Val247Ile missense_variant Exon 8 of 10 1 NM_013442.3 ENSP00000348886.5 Q9UJZ1-1
STOML2ENST00000452248.6 linkc.604G>A p.Val202Ile missense_variant Exon 7 of 9 2 ENSP00000395743.2 Q9UJZ1-2
STOML2ENST00000619795.4 linkc.601G>A p.Val201Ile missense_variant Exon 7 of 9 3 ENSP00000481672.1 A0A087WYB4
STOML2ENST00000488050.1 linkn.172G>A non_coding_transcript_exon_variant Exon 3 of 4 5 ENSP00000434531.1 F2Z2I8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461702
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.739G>A (p.V247I) alteration is located in exon 8 (coding exon 8) of the STOML2 gene. This alteration results from a G to A substitution at nucleotide position 739, causing the valine (V) at amino acid position 247 to be replaced by an isoleucine (I). 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
Benign
0.071
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
18
DANN
Benign
0.87
DEOGEN2
Benign
0.0027
.;T;T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.075
T;T;T
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
-1.3
.;.;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.31
N;.;N
REVEL
Benign
0.28
Sift
Benign
1.0
T;.;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0010
.;.;B
Vest4
0.22
MVP
0.38
MPC
0.68
ClinPred
0.13
T
GERP RS
5.2
Varity_R
0.025
gMVP
0.50

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.

Other links and lift over

dbSNP: rs769316607; hg19: chr9-35100994; COSMIC: COSV53052562; COSMIC: COSV53052562; API