2-241871817-C-A

Variant names:

• chr2-241871817-C-A
• NM_173821.3:c.262C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173821.3(RTP5):​c.262C>A​(p.Arg88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88H) 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.731

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTP5	NM_173821.3	c.262C>A	p.Arg88Ser	missense_variant	Exon 2 of 2	ENST00000343216.3	NP_776182.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTP5	ENST00000343216.3	c.262C>A	p.Arg88Ser	missense_variant	Exon 2 of 2	1	NM_173821.3	ENSP00000345374.3
RTP5	ENST00000419912.1	n.*275C>A		non_coding_transcript_exon_variant	Exon 3 of 3	5		ENSP00000397191.1
RTP5	ENST00000419912.1	n.*275C>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000397191.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414258 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 699592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262C>A (p.R88S) alteration is located in exon 2 (coding exon 2) of the RTP5 gene. This alteration results from a C to A substitution at nucleotide position 262, causing the arginine (R) at amino acid position 88 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0046	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.90		Loss of MoRF binding (P = 0.0393);
MVP		0.12
MPC		0.51
ClinPred		0.96	D
GERP RS		0.94
Varity_R		0.70
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-242813969;