4-158617148-T-A

Variant summary

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

The NM_021634.4(RXFP1):c.698T>A(p.Val233Asp) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V233F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RXFP1 NM_021634.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

Genes affected

RXFP1 (HGNC:19718): (relaxin family peptide receptor 1) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane receptor superfamily. The encoded protein plays a critical role in sperm motility, pregnancy and parturition as a receptor for the protein hormone relaxin. Decreased expression of this gene may play a role in endometriosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

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=0.19980907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXFP1	NM_021634.4	c.698T>A	p.Val233Asp	missense_variant	9/18	ENST00000307765.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXFP1	ENST00000307765.10	c.698T>A	p.Val233Asp	missense_variant	9/18	1	NM_021634.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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

Jan 23, 2024

The c.698T>A (p.V233D) alteration is located in exon 9 (coding exon 9) of the RXFP1 gene. This alteration results from a T to A substitution at nucleotide position 698, causing the valine (V) at amino acid position 233 to be replaced by an aspartic acid (D). 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	0.097
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	17
Dann	Benign	0.95
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.32	T;T;T;T;T;D;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.97	N;.;.;.;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.20	T;.;.;.;T;T;T
Sift4G	Benign	0.22	T;.;T;T;T;T;T
Polyphen		0.0	B;.;B;.;B;B;B
Vest4		0.38
MutPred		0.57		.;.;.;.;Gain of disorder (P = 0.0775);Gain of disorder (P = 0.0775);.;
MVP		0.74
MPC		0.24
ClinPred		0.44	T
GERP RS		2.3
Varity_R		0.13
gMVP		0.46

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: chr4-159538300;