X-47089855-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152869.4(RGN):​c.426C>G​(p.His142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 108,642 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: š‘“ 0.000018 ( 0 hom., 1 hem., cov: 20)

Consequence

RGN
NM_152869.4 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030187607).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGNNM_152869.4 linkc.426C>G p.His142Gln 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.426C>G p.His142Gln missense_variant Exon 5 of 8 5 NM_152869.4 ENSP00000380365.1 Q15493-1

Frequencies

GnomAD3 genomes
AF:
0.0000184
AC:
2
AN:
108642
Hom.:
0
Cov.:
20
AF XY:
0.0000322
AC XY:
1
AN XY:
31010
show subpopulations
Gnomad AFR
AF:
0.0000671
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
AF:
0.0000184
AC:
2
AN:
108642
Hom.:
0
Cov.:
20
AF XY:
0.0000322
AC XY:
1
AN XY:
31010
show subpopulations
Gnomad4 AFR
AF:
0.0000671
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.0020
DANN
Benign
0.66
DEOGEN2
Benign
0.11
T;T;T
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.16
T;.;.
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.88
N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.78
N;N;N
REVEL
Benign
0.048
Sift
Benign
0.090
T;T;T
Sift4G
Benign
0.47
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.085
MutPred
0.38
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.29
MPC
0.017
ClinPred
0.10
T
GERP RS
-11
Varity_R
0.21
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs201477424; hg19: chrX-46949254; API