20-58995183-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000681011(CTSZ):​c.*466T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 169,292 control chromosomes in the GnomAD database, including 32,030 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 0.61 ( 28821 hom., cov: 31)
Exomes 𝑓: 0.59 ( 3209 hom. )

Consequence

CTSZ
ENST00000681011 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793
Variant links:
Genes affected
CTSZ (HGNC:2547): (cathepsin Z) The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]
NELFCD (HGNC:15934): (negative elongation factor complex member C/D) The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NELFCDNM_198976.4 linkc.*507A>G downstream_gene_variant ENST00000652272.2 NP_945327.3 Q8IXH7-4H0UI80
CTSZNM_001336.4 linkc.*466T>C downstream_gene_variant ENST00000217131.6 NP_001327.2 Q9UBR2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NELFCDENST00000652272.2 linkc.*507A>G downstream_gene_variant NM_198976.4 ENSP00000499018.1 Q8IXH7-4
CTSZENST00000217131.6 linkc.*466T>C downstream_gene_variant 1 NM_001336.4 ENSP00000217131.5 Q9UBR2

Frequencies

GnomAD3 genomes
AF:
0.613
AC:
93123
AN:
151818
Hom.:
28813
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.558
Gnomad AMI
AF:
0.712
Gnomad AMR
AF:
0.589
Gnomad ASJ
AF:
0.610
Gnomad EAS
AF:
0.788
Gnomad SAS
AF:
0.646
Gnomad FIN
AF:
0.593
Gnomad MID
AF:
0.491
Gnomad NFE
AF:
0.640
Gnomad OTH
AF:
0.599
GnomAD4 exome
AF:
0.589
AC:
10227
AN:
17356
Hom.:
3209
Cov.:
0
AF XY:
0.583
AC XY:
5122
AN XY:
8782
show subpopulations
African (AFR)
AF:
0.518
AC:
265
AN:
512
American (AMR)
AF:
0.523
AC:
779
AN:
1490
Ashkenazi Jewish (ASJ)
AF:
0.588
AC:
301
AN:
512
East Asian (EAS)
AF:
0.810
AC:
515
AN:
636
South Asian (SAS)
AF:
0.600
AC:
831
AN:
1386
European-Finnish (FIN)
AF:
0.523
AC:
301
AN:
576
Middle Eastern (MID)
AF:
0.523
AC:
23
AN:
44
European-Non Finnish (NFE)
AF:
0.594
AC:
6672
AN:
11240
Other (OTH)
AF:
0.563
AC:
540
AN:
960
Heterozygous variant carriers
0
199
397
596
794
993
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
78
156
234
312
390
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.613
AC:
93180
AN:
151936
Hom.:
28821
Cov.:
31
AF XY:
0.610
AC XY:
45327
AN XY:
74246
show subpopulations
African (AFR)
AF:
0.558
AC:
23097
AN:
41412
American (AMR)
AF:
0.588
AC:
8978
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.610
AC:
2114
AN:
3464
East Asian (EAS)
AF:
0.788
AC:
4076
AN:
5170
South Asian (SAS)
AF:
0.647
AC:
3117
AN:
4816
European-Finnish (FIN)
AF:
0.593
AC:
6232
AN:
10506
Middle Eastern (MID)
AF:
0.510
AC:
150
AN:
294
European-Non Finnish (NFE)
AF:
0.640
AC:
43502
AN:
67990
Other (OTH)
AF:
0.599
AC:
1266
AN:
2114
Heterozygous variant carriers
0
1820
3640
5461
7281
9101
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
776
1552
2328
3104
3880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.615
Hom.:
35261
Bravo
AF:
0.612
Asia WGS
AF:
0.673
AC:
2345
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.14
DANN
Benign
0.36

Splicing

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.

Other links and lift over

dbSNP: rs448943; hg19: chr20-57570238; API