Genetic Variant NM_004388.3:c.545G>C (chr1-84565993-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004388.3(CTBS):c.545G>C(p.Trp182Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,438 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: 0.0000043 ( 0 hom. )

Consequence

CTBS
NM_004388.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3 link	c.545G>C	p.Trp182Ser	missense_variant	Exon 4 of 7	ENST00000370630.6	NP_004379.1	Q01459Q8TC97
SPATA1	NM_001397487.1 link	c.*104C>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000699524.1	NP_001384416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBS	ENST00000370630.6 link	c.545G>C	p.Trp182Ser	missense_variant	Exon 4 of 7	1	NM_004388.3	ENSP00000359664.4		Q01459
SPATA1	ENST00000699524.1 link	c.*104C>G		3_prime_UTR_variant	Exon 14 of 14		NM_001397487.1	ENSP00000514414.1		A0A8V8TNU4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000460

AC:

AN:

217326

Hom.:

AF XY:

0.00000845

AC XY:

AN XY:

118306

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000977

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1399438

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000771

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

Alfa

AF:

0.000224

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545G>C (p.W182S) alteration is located in exon 4 (coding exon 4) of the CTBS gene. This alteration results from a G to C substitution at nucleotide position 545, causing the tryptophan (W) at amino acid position 182 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-13

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.97

Vest4

0.86

MutPred

0.71

Gain of disorder (P = 0.0022);

MVP

0.60

MPC

0.46

ClinPred

1.0

GERP RS

5.0

Varity_R

0.97

gMVP

0.98

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over