NM_031440.2:c.161A>G

Variant names:

• chr3-46500361-A-G
• rs1382024874
• NM_031440.2:c.161A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031440.2(RTP3):​c.161A>G​(p.Gln54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. Q54P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RTP3 NM_031440.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 0 publications found

Genes affected

RTP3 (HGNC:15572): (receptor transporter protein 3) Predicted to enable olfactory receptor binding activity. Involved in detection of chemical stimulus involved in sensory perception of bitter taste and protein targeting to membrane. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2801565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031440.2. 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
	RTP3	NM_031440.2	MANE Select	c.161A>G	p.Gln54Arg	missense	Exon 2 of 2	NP_113628.1	Q9BQQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTP3	ENST00000296142.4	TSL:1 MANE Select	c.161A>G	p.Gln54Arg	missense	Exon 2 of 2	ENSP00000296142.3	Q9BQQ7
	RTP3	ENST00000684260.1		c.161A>G	p.Gln54Arg	missense	Exon 3 of 3	ENSP00000507138.1	Q9BQQ7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1452704 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 AN XY: 722410

African (AFR) AF: 0.00 AC: 0 AN: 33094

American (AMR) AF: 0.00 AC: 0 AN: 43730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 84730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4710

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1108404

Other (OTH) AF: 0.00 AC: 0 AN: 59906

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.94
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.059
Sift	Benign	0.49	T
Sift4G	Uncertain	0.025	D
Polyphen		0.47	P
Vest4		0.23
MutPred		0.61		Gain of MoRF binding (P = 0.0404)
MVP		0.26
MPC		0.12
ClinPred		0.10	T
GERP RS		0.94
Varity_R		0.062
gMVP		0.17
Mutation Taster		=89/11	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: rs1382024874; hg19: chr3-46541851;