13-38970325-C-G

Variant names:

• chr13-38970325-C-G
• NM_145286.3:c.376G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145286.3(STOML3):​c.376G>C​(p.Ala126Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STOML3 NM_145286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3729568).

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.376G>C	p.Ala126Pro	missense	Exon 5 of 7	NP_660329.1	Q8TAV4-1
	STOML3	NM_001144033.2		c.349G>C	p.Ala117Pro	missense	Exon 6 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.376G>C	p.Ala126Pro	missense	Exon 5 of 7	ENSP00000368952.4	Q8TAV4-1
	STOML3	ENST00000880988.1		c.376G>C	p.Ala126Pro	missense	Exon 5 of 7	ENSP00000551047.1
	STOML3	ENST00000423210.1	TSL:2	c.349G>C	p.Ala117Pro	missense	Exon 6 of 8	ENSP00000401989.1	Q8TAV4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Benign	0.72
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.28
Eigen_PC	Benign	0.0075
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.087	T
MutationAssessor	Benign	-0.38	N
PhyloP100		5.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.48
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.077	B
Vest4		0.44
MutPred		0.77		Gain of helix (P = 0.132)
MVP		0.65
MPC		0.43
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.72
Mutation Taster		=21/79	disease causing

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

hg19: chr13-39544462;