Genetic Variant NM_004388.3:c.998C>G (chr1-84555159-G-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_004388.3(CTBS):c.998C>G(p.Pro333Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CTBS
NM_004388.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.11

Publications

0 publications found

Variant links:

Genes affected

CTBS (HGNC:2496): (chitobiase) Chitobiase is a lysosomal glycosidase involved in degradation of asparagine-linked oligosaccharides on glycoproteins (Aronson and Kuranda, 1989 [PubMed 2531691]).[supplied by OMIM, Nov 2010]

CTBS links:

SPATA1 (HGNC:14682): (spermatogenesis associated 1)

SPATA1 links:

ENSG00000285851 (HGNC:):

ENSG00000285851 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004388.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBS	NM_004388.3	MANE Select	c.998C>G	p.Pro333Arg	missense	Exon 7 of 7	NP_004379.1	Q01459
SPATA1	NM_001397487.1	MANE Select	c.1225-751G>C		intron	N/A	NP_001384416.1	A0A8V8TNU4
SPATA1	NM_001310156.2		c.*1-751G>C		intron	N/A	NP_001297085.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBS	ENST00000370630.6	TSL:1 MANE Select	c.998C>G	p.Pro333Arg	missense	Exon 7 of 7	ENSP00000359664.4	Q01459
SPATA1	ENST00000699524.1	MANE Select	c.1225-751G>C		intron	N/A	ENSP00000514414.1	A0A8V8TNU4
CTBS	ENST00000477677.5	TSL:1	n.854C>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251306

AF XY:

0.00000736

show subpopulations

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:

0.00000889

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000128

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111870

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

PhyloP100

8.1

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-8.1

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.75

MutPred

0.88

Gain of MoRF binding (P = 0.0162)

MVP

0.65

MPC

0.38

ClinPred

0.98

GERP RS

5.6

Varity_R

0.91

gMVP

0.83

Mutation Taster

=41/59

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over