1-206012317-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001910.4(CTSE):c.1017C>T(p.Tyr339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,613,110 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (21 hom.)
• Consequence: CTSE NM_001910.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.78

Genes affected

CTSE (HGNC:2530): (cathepsin E) This gene encodes a member of the A1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme, an aspartic endopeptidase, may be involved in antigen processing and the maturation of secretory proteins. Elevated expression of this gene has been observed in neurodegeneration. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028101772).
• BP6: Variant 1-206012317-G-A is Benign according to our data. Variant chr1-206012317-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3078756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.78 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSE	NM_001910.4	c.1017C>T	p.Tyr339=	synonymous_variant	8/9	ENST00000358184.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSE	ENST00000358184.7	c.1017C>T	p.Tyr339=	synonymous_variant	8/9	1	NM_001910.4	P2

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152180 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00163 AC: 408 AN: 250996 Hom.: 2 AF XY: 0.00161 AC XY: 219 AN XY: 135650

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00697

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00219

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00217 AC: 3167 AN: 1460812 Hom.: 21 Cov.: 31 AF XY: 0.00213 AC XY: 1551 AN XY: 726786

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00230

Gnomad4 ASJ exome AF: 0.00628

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152298 Hom.: 1 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74460

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00243 Hom.: 7

Bravo AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.45
Cadd	Benign	6.3
Dann	Benign	0.95
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.028	T
PROVEAN	Benign	-0.51	N
Sift	Benign	0.044	D
Sift4G	Benign	0.27	T
Vest4		0.28

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

Other links and lift over

dbSNP: rs142068333; hg19: chr1-206329051;