3-187371143-A-G

Variant names:

• chr3-187371143-A-G
• NM_022147.3:c.511A>G

Variant summary

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

The NM_022147.3(RTP4):​c.511A>G​(p.Thr171Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RTP4 NM_022147.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.521

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

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=0.06906214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTP4	NM_022147.3	c.511A>G	p.Thr171Ala	missense_variant	Exon 2 of 2	ENST00000259030.3	NP_071430.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTP4	ENST00000259030.3	c.511A>G	p.Thr171Ala	missense_variant	Exon 2 of 2	1	NM_022147.3	ENSP00000259030.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 53 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511A>G (p.T171A) alteration is located in exon 2 (coding exon 2) of the RTP4 gene. This alteration results from a A to G substitution at nucleotide position 511, causing the threonine (T) at amino acid position 171 to be replaced by an alanine (A). 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	0.075
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.47
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.094
Sift	Benign	0.35	T
Sift4G	Benign	0.53	T
Polyphen		0.66	P
Vest4		0.025
MutPred		0.28		Loss of methylation at K175 (P = 0.0674);
MVP		0.25
MPC		0.13
ClinPred		0.19	T
GERP RS		-2.1
Varity_R		0.023
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-187088931;