3-187368491-A-C

Variant names:

• chr3-187368491-A-C
• rs749712353
• NM_022147.3:c.50A>C

Variant summary

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

The NM_022147.3(RTP4):​c.50A>C​(p.Gln17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. Q17R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTP4 NM_022147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 0 publications found

Genes affected

RTP4 (HGNC:23992): (receptor transporter protein 4) Predicted to enable olfactory receptor binding activity. Involved in defense response to virus; 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24580279).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022147.3. 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
	RTP4	NM_022147.3	MANE Select	c.50A>C	p.Gln17Pro	missense	Exon 1 of 2	NP_071430.2	Q96DX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTP4	ENST00000259030.3	TSL:1 MANE Select	c.50A>C	p.Gln17Pro	missense	Exon 1 of 2	ENSP00000259030.2	Q96DX8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.19
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.046	D
Polyphen		0.98	D
Vest4		0.38
MutPred		0.29		Gain of ubiquitination at K20 (P = 0.0898)
MVP		0.36
MPC		0.55
ClinPred		0.90	D
GERP RS		0.31
PromoterAI		0.022	Neutral
Varity_R		0.47
gMVP		0.59
Mutation Taster		=94/6	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: rs749712353; hg19: chr3-187086279;