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GeneBe

9-5339580-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006911.4(RLN1):c.167C>G(p.Ser56Cys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Consequence

RLN1
NM_006911.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78
Variant links:
Genes affected
RLN1 (HGNC:10026): (relaxin 1) Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In humans there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3, where RLN1 and RLN2 share high sequence homology. The protein encoded by this gene is synthesized as a single-chain polypeptide but the active form consists of an A chain and a B chain linked by disulfide bonds. Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility, regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. [provided by RefSeq, Jan 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31385702).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RLN1NM_006911.4 linkuse as main transcriptc.167C>G p.Ser56Cys missense_variant 1/2 ENST00000223862.2
RLN1XM_047423703.1 linkuse as main transcriptc.167C>G p.Ser56Cys missense_variant 1/3
RLN1XM_047423706.1 linkuse as main transcriptc.-48+1241C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLN1ENST00000223862.2 linkuse as main transcriptc.167C>G p.Ser56Cys missense_variant 1/21 NM_006911.4 P1P04808-1

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
27

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 submitterclinical testingAmbry GeneticsSep 14, 2022The c.167C>G (p.S56C) alteration is located in exon 1 (coding exon 1) of the RLN1 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by a cysteine (C). 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
0.22
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
Cadd
Benign
12
Dann
Uncertain
0.98
DEOGEN2
Pathogenic
0.81
D
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.0079
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.058
Sift
Uncertain
0.021
D
Sift4G
Uncertain
0.029
D
Polyphen
0.99
D
Vest4
0.16
MutPred
0.53
Loss of disorder (P = 0.0036);
MVP
0.23
MPC
0.27
ClinPred
0.86
D
GERP RS
-0.53
Varity_R
0.099
gMVP
0.13

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: chr9-5339580; API