chrX-47089812-A-G

Variant names:

• chrX-47089812-A-G
• NM_152869.4:c.383A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152869.4(RGN):​c.383A>G​(p.Glu128Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: RGN NM_152869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28
• Publications: 0 publications found

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]

ENSG00000307069 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGN	NM_152869.4	MANE Select	c.383A>G	p.Glu128Gly	missense	Exon 5 of 8	NP_690608.1	Q15493-1
	RGN	NM_004683.6		c.383A>G	p.Glu128Gly	missense	Exon 4 of 7	NP_004674.1	Q15493-1
	RGN	NM_001282848.2		c.224A>G	p.Glu75Gly	missense	Exon 5 of 8	NP_001269777.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGN	ENST00000397180.6	TSL:5 MANE Select	c.383A>G	p.Glu128Gly	missense	Exon 5 of 8	ENSP00000380365.1	Q15493-1
	RGN	ENST00000336169.3	TSL:1	c.383A>G	p.Glu128Gly	missense	Exon 4 of 7	ENSP00000338400.3	Q15493-1
	RGN	ENST00000352078.8	TSL:1	c.383A>G	p.Glu128Gly	missense	Exon 4 of 7	ENSP00000253303.4	Q15493-1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.082	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.49		Gain of sheet (P = 0.0827)
MVP		0.40
MPC		0.12
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.56
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-46949211;