NM_001910.4:c.319G>A

Variant names:

• chr1-206022174-C-T
• rs193920960
• NM_001910.4:c.319G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001910.4(CTSE):​c.319G>A​(p.Val107Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CTSE NM_001910.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.169
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26358634).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001910.4. 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
	CTSE	NM_001910.4	MANE Select	c.319G>A	p.Val107Met	missense	Exon 3 of 9	NP_001901.1	P14091-1
	CTSE	NM_148964.3		c.319G>A	p.Val107Met	missense	Exon 3 of 8	NP_683865.1	P14091-2
	CTSE	NM_001317331.2		c.94G>A	p.Val32Met	missense	Exon 2 of 7	NP_001304260.1	B4DNU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSE	ENST00000358184.7	TSL:1 MANE Select	c.319G>A	p.Val107Met	missense	Exon 3 of 9	ENSP00000350911.2	P14091-1
	CTSE	ENST00000360218.3	TSL:1	c.319G>A	p.Val107Met	missense	Exon 3 of 9	ENSP00000353350.3	A0A7P0MPN9
	CTSE	ENST00000678498.1		c.319G>A	p.Val107Met	missense	Exon 3 of 8	ENSP00000504305.1	P14091-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249548 AF XY: 0.00000742

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459076 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725888

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109904

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.26	T
PhyloP100		-0.17
PROVEAN	Benign	-1.9	N
Sift	Benign	0.051	T
Sift4G	Uncertain	0.012	D
Vest4		0.37
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193920960; hg19: chr1-206319194; COSMIC: COSV63062030; COSMIC: COSV63062030;