Variant rs13345 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004390.5(CTSH):c.459G>A(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,418 control chromosomes in the GnomAD database, including 36,517 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6576 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29941 hom. )

Consequence

CTSH
NM_004390.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.29

Variant links:

Genes affected

CTSH (HGNC:2535): (cathepsin H) The protein encoded by this gene is a lysosomal cysteine proteinase important in the overall degradation of lysosomal proteins. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. The encoded protein, which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. Increased expression of this gene has been correlated with malignant progression of prostate tumors. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

CTSH links:

CTSH (HGNC:):

CTSH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-7.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSH	NM_004390.5 linkuse as main transcript	c.459G>A	p.Ala153Ala	synonymous_variant	6/12	ENST00000220166.10	NP_004381.2	P09668
CTSH	NM_001411095.1 linkuse as main transcript	c.345G>A	p.Ala115Ala	synonymous_variant	6/12		NP_001398024.1
CTSH	XM_017021951.2 linkuse as main transcript	c.405G>A	p.Ala135Ala	synonymous_variant	7/13		XP_016877440.1
CTSH	NM_001319137.2 linkuse as main transcript	c.-479G>A		5_prime_UTR_variant	7/13		NP_001306066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166.10 linkuse as main transcript	c.459G>A	p.Ala153Ala	synonymous_variant	6/12	1	NM_004390.5	ENSP00000220166.6		P09668

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40878

AN:

151888

Hom.:

6572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.215

AC:

54046

AN:

251280

Hom.:

6676

AF XY:

0.210

AC XY:

28573

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.194

AC:

283877

AN:

1461412

Hom.:

29941

Cov.:

AF XY:

0.193

AC XY:

140195

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.269

AC:

40915

AN:

152006

Hom.:

6576

Cov.:

AF XY:

0.266

AC XY:

19729

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.219

Hom.:

2951

Bravo

AF:

0.282

Asia WGS

AF:

0.238

AC:

830

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.47

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over