Variant chr19-14028314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080864.4(RLN3):c.110G>A(p.Arg37Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RLN3
NM_080864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.77

Variant links:

Genes affected

RLN3 (HGNC:17135): (relaxin 3) This gene encodes a member of the relaxin family of insulin-like hormones that is expressed predominantly in the brain and plays a role in physiological processes such as stress, memory and appetite regulation. The encoded protein is a precursor that is proteolytically processed to generate a heterodimeric mature form consisting A and B chains interlinked by disulfide bonds. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]

RLN3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLN3	NM_080864.4 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	1/2	ENST00000431365.3	NP_543140.1	Q8WXF3B2RU28
RLN3	NM_001311197.2 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	1/3		NP_001298126.1	Q8WXF3K7ENX1B2RU28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLN3	ENST00000431365.3 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	1/2	1	NM_080864.4	ENSP00000397415.2		Q8WXF3
RLN3	ENST00000585987.1 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	1/3	1		ENSP00000467130.1		K7ENX1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251120

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Sep 02, 2024

The c.110G>A (p.R37Q) alteration is located in exon 1 (coding exon 1) of the RLN3 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the arginine (R) at amino acid position 37 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

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.91

D;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Pathogenic

0.89

MutationAssessor

Pathogenic

3.3

M;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.6

D;.

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.74

Loss of MoRF binding (P = 0.0112);Loss of MoRF binding (P = 0.0112);

MVP

0.87

MPC

0.41

ClinPred

0.96

GERP RS

4.6

Varity_R

0.96

gMVP

0.83

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