X-47089791-A-G

Variant names:

• chrX-47089791-A-G
• rs1428651510
• NM_152869.4:c.362A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3135596).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.362A>G	p.Glu121Gly	missense	Exon 5 of 8	NP_690608.1	Q15493-1
	RGN	NM_004683.6		c.362A>G	p.Glu121Gly	missense	Exon 4 of 7	NP_004674.1	Q15493-1
	RGN	NM_001282848.2		c.203A>G	p.Glu68Gly	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.362A>G	p.Glu121Gly	missense	Exon 5 of 8	ENSP00000380365.1	Q15493-1
	RGN	ENST00000336169.3	TSL:1	c.362A>G	p.Glu121Gly	missense	Exon 4 of 7	ENSP00000338400.3	Q15493-1
	RGN	ENST00000352078.8	TSL:1	c.362A>G	p.Glu121Gly	missense	Exon 4 of 7	ENSP00000253303.4	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

African (AFR) AF: 0.00 AC: 0 AN: 26290

American (AMR) AF: 0.00 AC: 0 AN: 34886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19234

East Asian (EAS) AF: 0.00 AC: 0 AN: 30013

South Asian (SAS) AF: 0.00 AC: 0 AN: 53523

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40381

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 839823

Other (OTH) AF: 0.00 AC: 0 AN: 45902

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	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
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.088
Sift	Benign	0.086	T
Sift4G	Uncertain	0.015	D
Polyphen		0.070	B
Vest4		0.40
MutPred		0.61		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
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1428651510; hg19: chrX-46949190;