9-35100997-C-T

Variant names:

• chr9-35100997-C-T
• rs769316607
• NM_013442.3:c.739G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

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)

ACMG classification

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
STOML2	NM_013442.3	c.739G>A	p.Val247Ile	missense_variant	Exon 8 of 10	ENST00000356493.10	NP_038470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOML2	ENST00000356493.10	c.739G>A	p.Val247Ile	missense_variant	Exon 8 of 10	1	NM_013442.3	ENSP00000348886.5
STOML2	ENST00000452248.6	c.604G>A	p.Val202Ile	missense_variant	Exon 7 of 9	2		ENSP00000395743.2
STOML2	ENST00000619795.4	c.601G>A	p.Val201Ile	missense_variant	Exon 7 of 9	3		ENSP00000481672.1
STOML2	ENST00000488050.1	n.172G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000434531.1

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

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

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

Other links and lift over

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