chr1-84563754-G-T

Variant names:

• chr1-84563754-G-T
• NM_004388.3:c.776C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004388.3(CTBS):​c.776C>A​(p.Thr259Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CTBS NM_004388.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.464
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21602994).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBS	NM_004388.3	MANE Select	c.776C>A	p.Thr259Asn	missense	Exon 5 of 7	NP_004379.1	Q01459
	SPATA1	NM_001397487.1	MANE Select	c.1295-2107G>T		intron	N/A	NP_001384416.1	A0A8V8TNU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBS	ENST00000370630.6	TSL:1 MANE Select	c.776C>A	p.Thr259Asn	missense	Exon 5 of 7	ENSP00000359664.4	Q01459
	SPATA1	ENST00000699524.1	MANE Select	c.1295-2107G>T		intron	N/A	ENSP00000514414.1	A0A8V8TNU4
	CTBS	ENST00000477677.5	TSL:1	n.632C>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448780 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721060

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.00 AC: 0 AN: 43624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 39096

South Asian (SAS) AF: 0.00 AC: 0 AN: 84394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5552

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104300

Other (OTH) AF: 0.00 AC: 0 AN: 59750

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.46
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.017
Sift	Benign	0.20	T
Sift4G	Benign	0.28	T
Polyphen		0.33	B
Vest4		0.33
MutPred		0.41		Gain of catalytic residue at T259 (P = 0.059)
MVP		0.20
MPC		0.17
ClinPred		0.18	T
GERP RS		2.6
Varity_R		0.033
gMVP		0.72
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr1-85029437;