X-47089855-C-G

Variant names:

• chrX-47089855-C-G
• rs201477424
• NM_152869.4:c.426C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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: 𝑓 0.000018 (0 hom., 1 hem., cov: 20)
• Consequence: RGN NM_152869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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]

ACMG classification

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
RGN	NM_152869.4	c.426C>G	p.His142Gln	missense_variant	Exon 5 of 8	ENST00000397180.6	NP_690608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGN	ENST00000397180.6	c.426C>G	p.His142Gln	missense_variant	Exon 5 of 8	5	NM_152869.4	ENSP00000380365.1

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 2 AN: 108642 Hom.: 0 Cov.: 20 AF XY: 0.0000322 AC XY: 1 AN XY: 31010

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

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

Other links and lift over

dbSNP: rs201477424; hg19: chrX-46949254;