Genetic Variant STOML3:p.Glu259Lys (chr13-38966926-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_145286.3(STOML3):c.775G>A(p.Glu259Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,890 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

STOML3
NM_145286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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]

STOML3 links:

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=0.24038675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOML3	NM_145286.3 link	c.775G>A	p.Glu259Lys	missense_variant	Exon 7 of 7	ENST00000379631.9	NP_660329.1	Q8TAV4-1
STOML3	NM_001144033.2 link	c.748G>A	p.Glu250Lys	missense_variant	Exon 8 of 8		NP_001137505.1	Q8TAV4-2
STOML3	XM_017020400.1 link	c.562G>A	p.Glu188Lys	missense_variant	Exon 5 of 5		XP_016875889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOML3	ENST00000379631.9 link	c.775G>A	p.Glu259Lys	missense_variant	Exon 7 of 7	1	NM_145286.3	ENSP00000368952.4		Q8TAV4-1
STOML3	ENST00000423210.1 link	c.748G>A	p.Glu250Lys	missense_variant	Exon 8 of 8	2		ENSP00000401989.1		Q8TAV4-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000839

AC:

AN:

250390

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000670

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.775G>A (p.E259K) alteration is located in exon 7 (coding exon 7) of the STOML3 gene. This alteration results from a G to A substitution at nucleotide position 775, causing the glutamic acid (E) at amino acid position 259 to be replaced by a lysine (K). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.24

T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.35

B;.

Vest4

0.14

MVP

0.73

MPC

0.075

ClinPred

0.29

GERP RS

3.7

Varity_R

0.22

gMVP

0.75

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.

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