NM_003793.4:c.1401T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003793.4(CTSF):c.1401T>C(p.Arg467Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,613,410 control chromosomes in the GnomAD database, including 244,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 29741 hom., cov: 33)

Exomes 𝑓: 0.54 ( 214618 hom. )

Consequence

CTSF
NM_003793.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.01

Publications

32 publications found

Variant links:

Genes affected

CTSF (HGNC:2531): (cathepsin F) Cathepsins are papain family cysteine proteinases that represent a major component of the lysosomal proteolytic system. Cathepsins generally contain a signal sequence, followed by a propeptide and then a catalytically active mature region. The very long (251 amino acid residues) proregion of the cathepsin F precursor contains a C-terminal domain similar to the pro-segment of cathepsin L-like enzymes, a 50-residue flexible linker peptide, and an N-terminal domain predicted to adopt a cystatin-like fold. The cathepsin F proregion is unique within the papain family cysteine proteases in that it contains this additional N-terminal segment predicted to share structural similarities with cysteine protease inhibitors of the cystatin superfamily. This cystatin-like domain contains some of the elements known to be important for inhibitory activity. CTSF encodes a predicted protein of 484 amino acids which contains a 19 residue signal peptide. Cathepsin F contains five potential N-glycosylation sites, and it may be targeted to the endosomal/lysosomal compartment via the mannose 6-phosphate receptor pathway. The cathepsin F gene is ubiquitously expressed, and it maps to chromosome 11q13, close to the gene encoding cathepsin W. [provided by RefSeq, Jul 2008]

CTSF Gene-Disease associations (from GenCC):

adult neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronal ceroid lipofuscinosis 13
Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

CTSF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-66563987-A-G is Benign according to our data. Variant chr11-66563987-A-G is described in ClinVar as Benign. ClinVar VariationId is 259168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003793.4. 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
	CTSF	NM_003793.4	MANE Select	c.1401T>C	p.Arg467Arg	synonymous	Exon 13 of 13	NP_003784.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTSF	ENST00000310325.10	TSL:1 MANE Select	c.1401T>C	p.Arg467Arg	synonymous	Exon 13 of 13	ENSP00000310832.5	Q9UBX1
CTSF	ENST00000679347.1		c.1496T>C	p.Val499Ala	missense	Exon 13 of 13	ENSP00000503676.1	A0A7I2YQH8
CTSF	ENST00000677005.1		c.1493T>C	p.Val498Ala	missense	Exon 13 of 13	ENSP00000503238.1	A0A7I2V313

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92535

AN:

151964

Hom.:

29684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.521

AC:

130253

AN:

250108

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.544

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.634

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.537

AC:

784612

AN:

1461328

Hom.:

214618

Cov.:

AF XY:

0.534

AC XY:

388057

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.839

AC:

28084

AN:

33474

American (AMR)

AF:

0.342

AC:

15267

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

14033

AN:

26132

East Asian (EAS)

AF:

0.511

AC:

20298

AN:

39688

South Asian (SAS)

AF:

0.402

AC:

34647

AN:

86234

European-Finnish (FIN)

AF:

0.631

AC:

33496

AN:

53090

Middle Eastern (MID)

AF:

0.516

AC:

2955

AN:

5722

European-Non Finnish (NFE)

AF:

0.542

AC:

603137

AN:

1111908

Other (OTH)

AF:

0.542

AC:

32695

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

24159

48318

72478

96637

120796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17066

34132

51198

68264

85330

<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:

0.609

AC:

92641

AN:

152082

Hom.:

29741

Cov.:

AF XY:

0.605

AC XY:

44967

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.825

AC:

34214

AN:

41490

American (AMR)

AF:

0.446

AC:

6821

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1830

AN:

3468

East Asian (EAS)

AF:

0.531

AC:

2738

AN:

5160

South Asian (SAS)

AF:

0.396

AC:

1910

AN:

4826

European-Finnish (FIN)

AF:

0.634

AC:

6710

AN:

10578

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36657

AN:

67960

Other (OTH)

AF:

0.575

AC:

1210

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1766

3532

5299

7065

8831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.573

Hom.:

37938

Bravo

AF:

0.607

Asia WGS

AF:

0.491

AC:

1709

AN:

3478

EpiCase

AF:

0.541

EpiControl

AF:

0.540

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neuronal ceroid lipofuscinosis 13 (4)

not provided (4)

not specified (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

(source)

DANN

Benign

0.59

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over