NM_152869.4:c.404A>T

Variant names:

• chrX-47089833-A-T
• rs782137920
• NM_152869.4:c.404A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_152869.4(RGN):​c.404A>T​(p.Tyr135Phe) variant causes a missense change. 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)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: RGN NM_152869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97
• 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 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

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.404A>T	p.Tyr135Phe	missense	Exon 5 of 8	NP_690608.1	Q15493-1
	RGN	NM_004683.6		c.404A>T	p.Tyr135Phe	missense	Exon 4 of 7	NP_004674.1	Q15493-1
	RGN	NM_001282848.2		c.245A>T	p.Tyr82Phe	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.404A>T	p.Tyr135Phe	missense	Exon 5 of 8	ENSP00000380365.1	Q15493-1
	RGN	ENST00000336169.3	TSL:1	c.404A>T	p.Tyr135Phe	missense	Exon 4 of 7	ENSP00000338400.3	Q15493-1
	RGN	ENST00000352078.8	TSL:1	c.404A>T	p.Tyr135Phe	missense	Exon 4 of 7	ENSP00000253303.4	Q15493-1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181668 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096964 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1 AN XY: 362386

African (AFR) AF: 0.00 AC: 0 AN: 26363

American (AMR) AF: 0.00 AC: 0 AN: 35121

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30134

South Asian (SAS) AF: 0.00 AC: 0 AN: 53971

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40451

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841406

Other (OTH) AF: 0.00 AC: 0 AN: 46033

GnomAD4 genome Cov.: 19

ExAC AF: 0.0000165 AC: 2

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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.74	D
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0052	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.22	T
Sift4G	Benign	0.24	T
Polyphen		0.041	B
Vest4		0.51
MutPred		0.82		Loss of phosphorylation at Y135 (P = 0.0517)
MVP		0.42
MPC		0.023
ClinPred		0.46	T
GERP RS		4.3
Varity_R		0.51
gMVP		0.57
Mutation Taster		=66/34	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: rs782137920; hg19: chrX-46949232;