Variant 15-78922996-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000220166.10(CTSH):c.929A>T(p.Asn310Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CTSH
ENST00000220166.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CTSH	NM_004390.5 linkuse as main transcript	c.929A>T	p.Asn310Ile	missense_variant	11/12	ENST00000220166.10	NP_004381.2
CTSH	NM_001411095.1 linkuse as main transcript	c.815A>T	p.Asn272Ile	missense_variant	11/12		NP_001398024.1
CTSH	NM_001319137.2 linkuse as main transcript	c.527A>T	p.Asn176Ile	missense_variant	12/13		NP_001306066.1
CTSH	XM_017021951.2 linkuse as main transcript	c.875A>T	p.Asn292Ile	missense_variant	12/13		XP_016877440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166.10 linkuse as main transcript	c.929A>T	p.Asn310Ile	missense_variant	11/12	1	NM_004390.5	ENSP00000220166	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457158

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.929A>T (p.N310I) alteration is located in exon 11 (coding exon 11) of the CTSH gene. This alteration results from a A to T substitution at nucleotide position 929, causing the asparagine (N) at amino acid position 310 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.92

D;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.7

H;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.016

D;D

Polyphen

0.86

P;.

Vest4

0.51

MutPred

0.57

Gain of catalytic residue at N310 (P = 0.1191);.;

MVP

0.18

MPC

0.46

ClinPred

0.92

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over