NM_022147.3:c.361C>T

Variant names:

• chr3-187370993-C-T
• rs1035105579
• NM_022147.3:c.361C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022147.3(RTP4):​c.361C>T​(p.His121Tyr) 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. 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. H121D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RTP4 NM_022147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047245264).

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.361C>T	p.His121Tyr	missense	Exon 2 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.361C>T	p.His121Tyr	missense	Exon 2 of 2	ENSP00000259030.2	Q96DX8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.89
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		0.034
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.048
Sift	Benign	0.24	T
Sift4G	Benign	0.24	T
Polyphen		0.0040	B
Vest4		0.062
MutPred		0.34		Loss of methylation at K124 (P = 0.0605)
MVP		0.24
MPC		0.16
ClinPred		0.067	T
GERP RS		1.9
Varity_R		0.074
gMVP		0.16
Mutation Taster		=100/0	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: rs1035105579; hg19: chr3-187088781;