3-187698689-C-G

Variant names:

• chr3-187698689-C-G
• rs780808305
• NM_001004312.2:c.487G>C

Variant summary

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

The NM_001004312.2(RTP2):​c.487G>C​(p.Val163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. V163I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RTP2 NM_001004312.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 3 publications found

Genes affected

RTP2 (HGNC:32486): (receptor transporter protein 2) Enables olfactory receptor binding activity. Involved in protein insertion into membrane. Located in cell surface. [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=0.09958413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004312.2. 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
	RTP2	NM_001004312.2	MANE Select	c.487G>C	p.Val163Leu	missense	Exon 2 of 2	NP_001004312.2	Q5QGT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTP2	ENST00000358241.1	TSL:1 MANE Select	c.487G>C	p.Val163Leu	missense	Exon 2 of 2	ENSP00000350976.1	Q5QGT7
	RTP2	ENST00000950650.1		c.487G>C	p.Val163Leu	missense	Exon 3 of 3	ENSP00000620709.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251210 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461742 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.42
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.046
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.055	B
Vest4		0.079
MutPred		0.67		Gain of sheet (P = 0.1208)
MVP		0.040
MPC		0.043
ClinPred		0.072	T
GERP RS		1.2
Varity_R		0.11
gMVP		0.51
Mutation Taster		=93/7	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: rs780808305; hg19: chr3-187416477;