13-31758269-A-C

Variant names:

• chr13-31758269-A-C
• NM_130806.5:c.106A>C

Variant summary

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

The NM_130806.5(RXFP2):​c.106A>C​(p.Thr36Pro) 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. 14/22 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: RXFP2 NM_130806.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0900
• Publications: 0 publications found

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

RXFP2 Gene-Disease associations (from GenCC):

• cryptorchidism

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=0.10243058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 17		NP_001159530.1
RXFP2	XM_017020389.2	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 18	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.106A>C	p.Thr36Pro	missense_variant	Exon 2 of 17	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106A>C (p.T36P) alteration is located in exon 2 (coding exon 2) of the RXFP2 gene. This alteration results from a A to C substitution at nucleotide position 106, causing the threonine (T) at amino acid position 36 to be replaced by a proline (P). 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	0.064
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		-0.090
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.96	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.069	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0	.;B
Vest4		0.36
MutPred		0.39		Gain of catalytic residue at S39 (P = 0);Gain of catalytic residue at S39 (P = 0);
MVP		0.61
MPC		0.29
ClinPred		0.087	T
GERP RS		0.21
Varity_R		0.25
gMVP		0.32
Mutation Taster		=92/8	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

hg19: chr13-32332406;