chr4-158651775-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021634.4(RXFP1):c.1994T>C(p.Val665Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,610,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RXFP1
NM_021634.4 missense
NM_021634.4 missense
Scores
4
8
5
Clinical Significance
Conservation
PhyloP100: 7.84
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RXFP1 | NM_021634.4 | c.1994T>C | p.Val665Ala | missense_variant | 18/18 | ENST00000307765.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RXFP1 | ENST00000307765.10 | c.1994T>C | p.Val665Ala | missense_variant | 18/18 | 1 | NM_021634.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247248Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134124
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GnomAD4 exome AF: 0.0000165 AC: 24AN: 1458650Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15AN XY: 725416
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2024 | The c.1994T>C (p.V665A) alteration is located in exon 18 (coding exon 18) of the RXFP1 gene. This alteration results from a T to C substitution at nucleotide position 1994, causing the valine (V) at amino acid position 665 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;.;.;D;D;D
REVEL
Benign
Sift
Uncertain
D;.;.;.;D;D;D
Sift4G
Uncertain
D;.;D;D;D;D;D
Polyphen
P;.;D;.;D;D;D
Vest4
MutPred
0.30
.;.;.;.;Gain of catalytic residue at V665 (P = 0.1128);.;.;
MVP
MPC
0.65
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at