X-47089838-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152869.4(RGN):​c.409C>G​(p.Leu137Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,097,430 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)
Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

RGN
NM_152869.4 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97
Variant links:
Genes affected
RGN (HGNC:9989): (regucalcin) The protein encoded by this gene is a highly conserved, calcium-binding protein, that is preferentially expressed in the liver and kidney. It may have an important role in calcium homeostasis. Studies in rat indicate that this protein may also play a role in aging, as it shows age-associated down-regulation. This gene is part of a gene cluster on chromosome Xp11.3-Xp11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.38123193).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGNNM_152869.4 linkc.409C>G p.Leu137Val missense_variant Exon 5 of 8 ENST00000397180.6 NP_690608.1 Q15493-1V9HWF8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGNENST00000397180.6 linkc.409C>G p.Leu137Val missense_variant Exon 5 of 8 5 NM_152869.4 ENSP00000380365.1 Q15493-1

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD4 exome
AF:
0.00000547
AC:
6
AN:
1097430
Hom.:
0
Cov.:
29
AF XY:
0.00000827
AC XY:
3
AN XY:
362818
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:
0.0000370
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000475
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
19

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.409C>G (p.L137V) alteration is located in exon 5 (coding exon 3) of the RGN gene. This alteration results from a C to G substitution at nucleotide position 409, causing the leucine (L) at amino acid position 137 to be replaced by a valine (V). 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
0.19
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;T;T
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
T;.;.
M_CAP
Pathogenic
0.32
D
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.14
Sift
Benign
0.075
T;T;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.33
B;B;B
Vest4
0.34
MutPred
0.68
Loss of stability (P = 0.0137);Loss of stability (P = 0.0137);Loss of stability (P = 0.0137);
MVP
0.51
MPC
0.027
ClinPred
0.81
D
GERP RS
5.5
Varity_R
0.64
gMVP
0.44

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.

Other links and lift over

dbSNP: rs1556386592; hg19: chrX-46949237; COSMIC: COSV60275773; COSMIC: COSV60275773; API