X-47089791-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_152869.4(RGN):​c.362A>G​(p.Glu121Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,094,117 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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: 0.0000027 ( 0 hom. 2 hem. )

Consequence

RGN
NM_152869.4 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06
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 -3 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity RGN_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.3135596).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGNNM_152869.4 linkc.362A>G p.Glu121Gly 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.362A>G p.Glu121Gly missense_variant Exon 5 of 8 5 NM_152869.4 ENSP00000380365.1 Q15493-1

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD4 exome
AF:
0.00000274
AC:
3
AN:
1094117
Hom.:
0
Cov.:
29
AF XY:
0.00000556
AC XY:
2
AN XY:
359791
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000357
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
19
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
May 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.362A>G (p.E121G) alteration is located in exon 5 (coding exon 3) of the RGN gene. This alteration results from a A to G substitution at nucleotide position 362, causing the glutamic acid (E) at amino acid position 121 to be replaced by a glycine (G). 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
0.51
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.67
D;D;D
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.75
T;.;.
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;L
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Benign
0.088
Sift
Benign
0.086
T;T;T
Sift4G
Uncertain
0.015
D;D;D
Polyphen
0.070
B;B;B
Vest4
0.40
MutPred
0.61
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.50
MPC
0.017
ClinPred
0.80
D
GERP RS
3.0
Varity_R
0.47
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1428651510; hg19: chrX-46949190; API