Variant 4-158646870-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021634.4(RXFP1):c.1425T>G(p.His475Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RXFP1
NM_021634.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

Variant links:

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]

RXFP1 links:

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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	Protein	UniProt
RXFP1	NM_021634.4 link	c.1425T>G	p.His475Gln	missense_variant	16/18	ENST00000307765.10	NP_067647.2	Q9HBX9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXFP1	ENST00000307765.10 link	c.1425T>G	p.His475Gln	missense_variant	16/18	1	NM_021634.4	ENSP00000303248.5		Q9HBX9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249462

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 05, 2024

The c.1425T>G (p.H475Q) alteration is located in exon 16 (coding exon 16) of the RXFP1 gene. This alteration results from a T to G substitution at nucleotide position 1425, causing the histidine (H) at amino acid position 475 to be replaced by a glutamine (Q). 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

0.23

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.14

CADD

Benign

8.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

.;T;T;T;D;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.84

T;T;T;T;T;T;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.052

MutationAssessor

Uncertain

2.6

.;.;.;.;M;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.9

D;.;.;.;D;D;D

REVEL

Uncertain

0.49

Sift

Benign

0.048

D;.;.;.;T;T;T

Sift4G

Uncertain

0.0040

D;.;D;D;D;D;D

Polyphen

0.057

B;.;D;.;P;P;P

Vest4

0.76

MutPred

0.55

.;.;.;.;Gain of ubiquitination at K474 (P = 0.0846);.;.;

MVP

0.72

MPC

0.47

ClinPred

0.98

GERP RS

-5.3

Varity_R

0.59

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over