1-155942217-G-A

Position:

• chr1-155942217-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181885.3(RXFP4):​c.508G>A​(p.Ala170Thr) 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. 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: 32)
• Consequence: RXFP4 NM_181885.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

RXFP4 (HGNC:14666): (relaxin family peptide/INSL5 receptor 4) GPR100 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044626504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXFP4	NM_181885.3	c.508G>A	p.Ala170Thr	missense_variant	1/1	ENST00000368318.5	NP_871001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXFP4	ENST00000368318.5	c.508G>A	p.Ala170Thr	missense_variant	1/1	6	NM_181885.3	ENSP00000357301.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.508G>A (p.A170T) alteration is located in exon 1 (coding exon 1) of the RXFP4 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the alanine (A) at amino acid position 170 to be replaced by a threonine (T). 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	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.055	N
MutationTaster	Benign	0.78	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.032
Sift	Benign	0.51	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.083
MutPred		0.51		Gain of glycosylation at A170 (P = 0.0949);
MVP		0.23
MPC		0.23
ClinPred		0.066	T
GERP RS		1.5
Varity_R		0.026
gMVP		0.20

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: chr1-155912008;