17-74941725-C-A

Variant names:

• chr17-74941725-C-A
• rs1196766803
• NM_001272005.2:c.352C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001272005.2(OTOP3):​c.352C>A​(p.Leu118Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. 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. L118F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTOP3 NM_001272005.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 1 publications found

Genes affected

OTOP3 (HGNC:19658): (otopetrin 3) Predicted to enable proton channel activity. Predicted to be involved in proton transmembrane transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13191462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272005.2. 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
	OTOP3	NM_001272005.2	MANE Select	c.352C>A	p.Leu118Ile	missense	Exon 2 of 7	NP_001258934.1	Q7RTS5-2
	OTOP3	NM_178233.2		c.406C>A	p.Leu136Ile	missense	Exon 2 of 7	NP_839947.1	Q7RTS5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOP3	ENST00000328801.6	TSL:2 MANE Select	c.352C>A	p.Leu118Ile	missense	Exon 2 of 7	ENSP00000328090.5	Q7RTS5-2
	OTOP3	ENST00000956756.1		c.319C>A	p.Leu107Ile	missense	Exon 2 of 7	ENSP00000626815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.39
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.056
Sift	Benign	0.16	T
Polyphen		0.084	B
MutPred		0.31		Gain of MoRF binding (P = 0.2631)
MVP		0.13
MPC		0.17
ClinPred		0.41	T
GERP RS		4.7
Varity_R		0.079
gMVP		0.21

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: rs1196766803; hg19: chr17-72937820;