2-241871883-G-C

Variant names:

• chr2-241871883-G-C
• rs755794520
• NM_173821.3:c.328G>C

Variant summary

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

The NM_173821.3(RTP5):​c.328G>C​(p.Glu110Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,344 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. E110K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RTP5 NM_173821.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10790771).

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.328G>C	p.Glu110Gln	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.328G>C	p.Glu110Gln	missense	Exon 2 of 2	ENSP00000345374.3	Q14D33
	RTP5	ENST00000419912.1	TSL:5	n.*341G>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000397191.1	F8WB75
	RTP5	ENST00000419912.1	TSL:5	n.*341G>C		3_prime_UTR	Exon 3 of 3	ENSP00000397191.1	F8WB75

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401344 Hom.: 0 Cov.: 37 AF XY: 0.00000145 AC XY: 1 AN XY: 690510

African (AFR) AF: 0.00 AC: 0 AN: 32412

American (AMR) AF: 0.00 AC: 0 AN: 36138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24812

East Asian (EAS) AF: 0.00 AC: 0 AN: 37088

South Asian (SAS) AF: 0.00 AC: 0 AN: 80140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078832

Other (OTH) AF: 0.00 AC: 0 AN: 57882

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.087
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.040
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.036	D
Polyphen		0.97	D
Vest4		0.091
MutPred		0.32		Gain of disorder (P = 0.1325)
MVP		0.055
MPC		0.25
ClinPred		0.15	T
GERP RS		0.81
Varity_R		0.087
gMVP		0.48
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs755794520; hg19: chr2-242814035;