chr13-38972559-C-T

Variant summary

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

The NM_145286.3(STOML3):​c.265G>A​(p.Val89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

STOML3
NM_145286.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.564
Variant links:
Genes affected
STOML3 (HGNC:19420): (stomatin like 3) Predicted to act upstream of or within signal transduction. Predicted to be located in cilium and membrane raft. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14354444).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STOML3NM_145286.3 linkc.265G>A p.Val89Ile missense_variant Exon 4 of 7 ENST00000379631.9 NP_660329.1 Q8TAV4-1
STOML3NM_001144033.2 linkc.238G>A p.Val80Ile missense_variant Exon 5 of 8 NP_001137505.1 Q8TAV4-2
STOML3XM_017020400.1 linkc.52G>A p.Val18Ile missense_variant Exon 2 of 5 XP_016875889.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STOML3ENST00000379631.9 linkc.265G>A p.Val89Ile missense_variant Exon 4 of 7 1 NM_145286.3 ENSP00000368952.4 Q8TAV4-1
STOML3ENST00000423210.1 linkc.238G>A p.Val80Ile missense_variant Exon 5 of 8 2 ENSP00000401989.1 Q8TAV4-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
31
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:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251410
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461734
Hom.:
0
Cov.:
30
AF XY:
0.0000316
AC XY:
23
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
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:
0.0000216
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152290
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000494
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.265G>A (p.V89I) alteration is located in exon 4 (coding exon 4) of the STOML3 gene. This alteration results from a G to A substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 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
0.083
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.25
T;.
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.065
FATHMM_MKL
Benign
0.58
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Uncertain
0.79
D
MutationAssessor
Benign
0.32
N;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.25
N;N
REVEL
Uncertain
0.42
Sift
Benign
0.60
T;T
Sift4G
Benign
0.55
T;T
Polyphen
0.0020
B;.
Vest4
0.11
MutPred
0.27
Loss of methylation at K90 (P = 0.1016);.;
MVP
0.47
MPC
0.057
ClinPred
0.095
T
GERP RS
5.7
Varity_R
0.061
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs747673142; hg19: chr13-39546696; API