13-38968497-C-G

Variant names:

• chr13-38968497-C-G
• rs992448888
• NM_145286.3:c.554G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145286.3(STOML3):​c.554G>C​(p.Arg185Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R185Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STOML3 NM_145286.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145286.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOML3	NM_145286.3	MANE Select	c.554G>C	p.Arg185Pro	missense	Exon 6 of 7	NP_660329.1	Q8TAV4-1
	STOML3	NM_001144033.2		c.527G>C	p.Arg176Pro	missense	Exon 7 of 8	NP_001137505.1	Q8TAV4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOML3	ENST00000379631.9	TSL:1 MANE Select	c.554G>C	p.Arg185Pro	missense	Exon 6 of 7	ENSP00000368952.4	Q8TAV4-1
	STOML3	ENST00000880988.1		c.578G>C	p.Arg193Pro	missense	Exon 6 of 7	ENSP00000551047.1
	STOML3	ENST00000423210.1	TSL:2	c.527G>C	p.Arg176Pro	missense	Exon 7 of 8	ENSP00000401989.1	Q8TAV4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.86	D
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.64
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.50	P
Vest4		0.51
MutPred		0.64		Loss of MoRF binding (P = 0.0024)
MVP		0.35
MPC		0.14
ClinPred		0.96	D
GERP RS		-3.1
Varity_R		0.63
gMVP		0.87
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs992448888; hg19: chr13-39542634;