2-241871818-G-T

Variant names:

• chr2-241871818-G-T
• rs746911206
• NM_173821.3:c.263G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173821.3(RTP5):​c.263G>T​(p.Arg88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R88C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RTP5 NM_173821.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 0 publications found

Genes affected

RTP5 (HGNC:26585): (receptor transporter protein 5 (putative)) Predicted to enable olfactory receptor binding activity. Predicted to be involved in detection of chemical stimulus involved in sensory perception of bitter taste; protein insertion into membrane; and protein targeting to 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173821.3. 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
	RTP5	NM_173821.3	MANE Select	c.263G>T	p.Arg88Leu	missense	Exon 2 of 2	NP_776182.2	Q14D33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTP5	ENST00000343216.3	TSL:1 MANE Select	c.263G>T	p.Arg88Leu	missense	Exon 2 of 2	ENSP00000345374.3	Q14D33
	RTP5	ENST00000419912.1	TSL:5	n.*276G>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000397191.1	F8WB75
	RTP5	ENST00000419912.1	TSL:5	n.*276G>T		3_prime_UTR	Exon 3 of 3	ENSP00000397191.1	F8WB75

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412174 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 698300

African (AFR) AF: 0.00 AC: 0 AN: 32350

American (AMR) AF: 0.00 AC: 0 AN: 36596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24478

East Asian (EAS) AF: 0.00 AC: 0 AN: 37518

South Asian (SAS) AF: 0.00 AC: 0 AN: 80166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087702

Other (OTH) AF: 0.00 AC: 0 AN: 58306

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.057
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0052	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.31
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.89		Loss of MoRF binding (P = 0.0249)
MVP		0.44
MPC		0.25
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.71
gMVP		0.81
Mutation Taster		=91/9	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: rs746911206; hg19: chr2-242813970;