1-84565843-G-T

Variant names:

• chr1-84565843-G-T
• NM_004388.3:c.695C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004388.3(CTBS):​c.695C>A​(p.Thr232Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T232I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTBS NM_004388.3 missense, splice_region
• Scores: Splicing: ADA: 0.001111
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10843933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3	c.695C>A	p.Thr232Asn	missense_variant, splice_region_variant	Exon 4 of 7	ENST00000370630.6	NP_004379.1
SPATA1	NM_001397487.1	c.1295-18G>T		intron_variant	Intron 13 of 13	ENST00000699524.1	NP_001384416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBS	ENST00000370630.6	c.695C>A	p.Thr232Asn	missense_variant, splice_region_variant	Exon 4 of 7	1	NM_004388.3	ENSP00000359664.4
SPATA1	ENST00000699524.1	c.1295-18G>T		intron_variant	Intron 13 of 13		NM_001397487.1	ENSP00000514414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.695C>A (p.T232N) alteration is located in exon 4 (coding exon 4) of the CTBS gene. This alteration results from a C to A substitution at nucleotide position 695, causing the threonine (T) at amino acid position 232 to be replaced by an asparagine (N). 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	Benign	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.076
Sift	Benign	0.34	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.098
MutPred		0.44		Loss of catalytic residue at T232 (P = 0.1303);
MVP		0.34
MPC		0.072
ClinPred		0.058	T
GERP RS		1.8
Varity_R		0.044
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.024
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-85031526;