5-33937453-C-A

Variant names:

• chr5-33937453-C-A
• rs200499016
• NM_016568.3:c.713C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016568.3(RXFP3):​c.713C>A​(p.Thr238Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T238M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RXFP3 NM_016568.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 3 publications found

Genes affected

RXFP3 (HGNC:24883): (relaxin family peptide receptor 3) Predicted to enable G protein-coupled peptide receptor activity. Involved in positive regulation of cytokinesis. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016568.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP3	NM_016568.3	MANE Select	c.713C>A	p.Thr238Lys	missense	Exon 1 of 1	NP_057652.1	Q9NSD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP3	ENST00000330120.5	TSL:6 MANE Select	c.713C>A	p.Thr238Lys	missense	Exon 1 of 1	ENSP00000328708.3	Q9NSD7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.37
Sift	Benign	0.11	T
Sift4G	Benign	0.41	T
Polyphen		0.79	P
Vest4		0.87
MutPred		0.72		Gain of ubiquitination at T238 (P = 0.0258)
MVP		0.86
MPC		1.4
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.46
gMVP		0.73
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs200499016; hg19: chr5-33937558;