rs201514577

Variant names:

• chrX-47084562-A-G
• rs201514577
• NM_152869.4:c.308A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_152869.4(RGN):​c.308A>G​(p.Asn103Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,197,784 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 279 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., 10 hem., cov: 24)
  • Exomes 𝑓: 0.00073 (0 hom. 269 hem.)
• Consequence: RGN NM_152869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.05
• 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 -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89
• BS2: High Hemizygotes in GnomAd4 at 10 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.308A>G	p.Asn103Ser	missense	Exon 4 of 8	NP_690608.1	Q15493-1
	RGN	NM_004683.6		c.308A>G	p.Asn103Ser	missense	Exon 3 of 7	NP_004674.1	Q15493-1
	RGN	NM_001282848.2		c.149A>G	p.Asn50Ser	missense	Exon 4 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.308A>G	p.Asn103Ser	missense	Exon 4 of 8	ENSP00000380365.1	Q15493-1
	RGN	ENST00000336169.3	TSL:1	c.308A>G	p.Asn103Ser	missense	Exon 3 of 7	ENSP00000338400.3	Q15493-1
	RGN	ENST00000352078.8	TSL:1	c.308A>G	p.Asn103Ser	missense	Exon 3 of 7	ENSP00000253303.4	Q15493-1

Frequencies

GnomAD3 genomes AF: 0.000285 AC: 32 AN: 112405 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000129

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: 0.000526

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000324 AC: 51 AN: 157180 AF XY: 0.000459

Gnomad AFR exome AF: 0.0000890

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000697

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000734 AC: 797 AN: 1085379 Hom.: 0 Cov.: 29 AF XY: 0.000761 AC XY: 269 AN XY: 353657

African (AFR) AF: 0.0000765 AC: 2 AN: 26141

American (AMR) AF: 0.0000891 AC: 3 AN: 33652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19132

East Asian (EAS) AF: 0.00 AC: 0 AN: 29672

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 52071

European-Finnish (FIN) AF: 0.0000251 AC: 1 AN: 39801

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.000926 AC: 773 AN: 835106

Other (OTH) AF: 0.000372 AC: 17 AN: 45679

GnomAD4 genome AF: 0.000285 AC: 32 AN: 112405 Hom.: 0 Cov.: 24 AF XY: 0.000289 AC XY: 10 AN XY: 34553

African (AFR) AF: 0.000129 AC: 4 AN: 30969

American (AMR) AF: 0.00 AC: 0 AN: 10578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3597

South Asian (SAS) AF: 0.00 AC: 0 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6179

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000526 AC: 28 AN: 53275

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.000520 Hom.: 21

Bravo AF: 0.000355

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000743 AC: 5

ExAC AF: 0.000290 AC: 35

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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.88	D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		8.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MVP		0.54
MPC		0.13
ClinPred		0.64	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.79
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: rs201514577; hg19: chrX-46943961;