X-47089855-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152869.4(RGN):​c.426C>A​(p.His142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,205,453 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 52 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.000092 (0 hom. 51 hem.)
• Consequence: RGN NM_152869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014323086).
• BS2: High Hemizygotes in GnomAdExome4 at 51 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.426C>A	p.His142Gln	missense	Exon 5 of 8	NP_690608.1	Q15493-1
	RGN	NM_004683.6		c.426C>A	p.His142Gln	missense	Exon 4 of 7	NP_004674.1	Q15493-1
	RGN	NM_001282848.2		c.267C>A	p.His89Gln	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.426C>A	p.His142Gln	missense	Exon 5 of 8	ENSP00000380365.1	Q15493-1
	RGN	ENST00000336169.3	TSL:1	c.426C>A	p.His142Gln	missense	Exon 4 of 7	ENSP00000338400.3	Q15493-1
	RGN	ENST00000352078.8	TSL:1	c.426C>A	p.His142Gln	missense	Exon 4 of 7	ENSP00000253303.4	Q15493-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 5 AN: 108642 Hom.: 0 Cov.: 20

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: 0.000390

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000380

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 22 AN: 182688 AF XY: 0.000253

Gnomad AFR exome AF: 0.0000762

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000921 AC: 101 AN: 1096811 Hom.: 0 Cov.: 29 AF XY: 0.000141 AC XY: 51 AN XY: 362213

African (AFR) AF: 0.00 AC: 0 AN: 26376

American (AMR) AF: 0.0000284 AC: 1 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30184

South Asian (SAS) AF: 0.000518 AC: 28 AN: 54067

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40483

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.0000809 AC: 68 AN: 840985

Other (OTH) AF: 0.0000869 AC: 4 AN: 46039

GnomAD4 genome AF: 0.0000460 AC: 5 AN: 108642 Hom.: 0 Cov.: 20 AF XY: 0.0000322 AC XY: 1 AN XY: 31010

African (AFR) AF: 0.0000671 AC: 2 AN: 29808

American (AMR) AF: 0.00 AC: 0 AN: 9748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3474

South Asian (SAS) AF: 0.000390 AC: 1 AN: 2566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000380 AC: 2 AN: 52629

Other (OTH) AF: 0.00 AC: 0 AN: 1441

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000109

EpiControl AF: 0.000298

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	0.094
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0010
DANN	Benign	0.78
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.88	N
PhyloP100		-1.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.78	N
REVEL	Benign	0.048
Sift	Benign	0.090	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.38		Loss of sheet (P = 0.0817)
MVP		0.29
MPC		0.017
ClinPred		0.035	T
GERP RS		-11
Varity_R		0.21
gMVP		0.26
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201477424; hg19: chrX-46949254;