9-121341236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004099.6(STOM):​c.833G>A​(p.Gly278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

STOM
NM_004099.6 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.91
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STOMNM_004099.6 linkc.833G>A p.Gly278Glu missense_variant Exon 7 of 7 ENST00000286713.7 NP_004090.4 P27105-1A0A024R882

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STOMENST00000286713.7 linkc.833G>A p.Gly278Glu missense_variant Exon 7 of 7 1 NM_004099.6 ENSP00000286713.2 P27105-1
STOMENST00000347359.3 linkc.338G>A p.Gly113Glu missense_variant Exon 3 of 3 2 ENSP00000339607.2 P27105-2
STOMENST00000538954.5 linkc.487-1595G>A intron_variant Intron 5 of 5 5 ENSP00000445764.2 F8VSL7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251396
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.0000179
AC XY:
13
AN XY:
727244
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:
0.0000162
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 23, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.833G>A (p.G278E) alteration is located in exon 7 (coding exon 7) of the STOM gene. This alteration results from a G to A substitution at nucleotide position 833, causing the glycine (G) at amino acid position 278 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.060
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;.
Eigen
Benign
-0.0022
Eigen_PC
Benign
0.0018
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.83
T;T
M_CAP
Pathogenic
0.52
D
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Pathogenic
0.68
Sift
Benign
0.18
T;T
Sift4G
Benign
0.33
T;T
Polyphen
0.37
B;.
Vest4
0.47
MVP
0.98
MPC
0.70
ClinPred
0.84
D
GERP RS
3.0
Varity_R
0.24
gMVP
0.94

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: rs369630995; hg19: chr9-124103514; API