Variant 9-121341353-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004099.6(STOM):c.716T>C(p.Met239Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0016 in 1,614,042 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 7 hom. )

Consequence

STOM
NM_004099.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

Variant links:

Genes affected

STOM (HGNC:3383): (stomatin) This gene encodes a member of a highly conserved family of integral membrane proteins. The encoded protein localizes to the cell membrane of red blood cells and other cell types, where it may regulate ion channels and transporters. Loss of localization of the encoded protein is associated with hereditary stomatocytosis, a form of hemolytic anemia. There is a pseudogene for this gene on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

STOM links:

STOM (HGNC:):

STOM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017136693).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOM	NM_004099.6 linkuse as main transcript	c.716T>C	p.Met239Thr	missense_variant	7/7	ENST00000286713.7	NP_004090.4	P27105-1A0A024R882

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STOM	ENST00000286713.7 linkuse as main transcript	c.716T>C	p.Met239Thr	missense_variant	7/7	1	NM_004099.6	ENSP00000286713.2	P27105-1
STOM	ENST00000347359.3 linkuse as main transcript	c.221T>C	p.Met74Thr	missense_variant	3/3	2		ENSP00000339607.2	P27105-2
STOM	ENST00000538954.5 linkuse as main transcript	c.487-1712T>C		intron_variant		5		ENSP00000445764.2	F8VSL7

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00144

AC:

362

AN:

251034

Hom.:

AF XY:

0.00153

AC XY:

208

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00165

AC:

2414

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1231

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152288

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00129

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00165

AC:

200

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00231

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;T

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.017

T;T

MetaSVM

Pathogenic

0.93

MutationAssessor

Benign

0.94

L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.37

Sift

Benign

0.35

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0

B;.

Vest4

0.26

MVP

0.92

MPC

0.46

ClinPred

0.027

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.81

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