2-241871883-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173821.3(RTP5):​c.328G>A​(p.Glu110Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,401,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: RTP5 NM_173821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0870

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09982559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTP5	NM_173821.3	c.328G>A	p.Glu110Lys	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.328G>A	p.Glu110Lys	missense_variant	Exon 2 of 2	1	NM_173821.3	ENSP00000345374.3
RTP5	ENST00000419912.1	n.*341G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5		ENSP00000397191.1
RTP5	ENST00000419912.1	n.*341G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000397191.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1401342 Hom.: 0 Cov.: 37 AF XY: 0.00000579 AC XY: 4 AN XY: 690508

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000539

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000851 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328G>A (p.E110K) alteration is located in exon 2 (coding exon 2) of the RTP5 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the glutamic acid (E) at amino acid position 110 to be replaced by a lysine (K). 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	Benign	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.054
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.054	T
Polyphen		0.97	D
Vest4		0.15
MVP		0.055
MPC		0.23
ClinPred		0.12	T
GERP RS		0.81
Varity_R		0.073
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs755794520; hg19: chr2-242814035;