chr9-121356150-G-A

Position:

• chr9-121356150-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004099.6(STOM):​c.68C>T​(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STOM NM_004099.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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 (HGNC:):

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=0.17716634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOM	NM_004099.6	c.68C>T	p.Pro23Leu	missense_variant	2/7	ENST00000286713.7	NP_004090.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOM	ENST00000286713.7	c.68C>T	p.Pro23Leu	missense_variant	2/7	1	NM_004099.6	ENSP00000286713.2
STOM	ENST00000538954.5	c.68C>T	p.Pro23Leu	missense_variant	2/6	5		ENSP00000445764.2
STOM	ENST00000347359.3	c.68C>T	p.Pro23Leu	missense_variant	2/3	2		ENSP00000339607.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.68C>T (p.P23L) alteration is located in exon 2 (coding exon 2) of the STOM gene. This alteration results from a C to T substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by a leucine (L). 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	0.091
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	.;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.20	T;T;D
Polyphen		0.0090	.;B;.
Vest4		0.24
MutPred		0.26		Loss of glycosylation at P23 (P = 0.0409);Loss of glycosylation at P23 (P = 0.0409);Loss of glycosylation at P23 (P = 0.0409);
MVP		0.92
MPC		0.41
ClinPred		0.28	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.071
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-124118428;