1-84563384-C-G

Variant names:

• chr1-84563384-C-G
• rs148118320
• NM_004388.3:c.830G>C

Variant summary

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

The NM_004388.3(CTBS):​c.830G>C​(p.Arg277Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,422,726 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTBS NM_004388.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.830G>C	p.Arg277Pro	missense	Exon 6 of 7	NP_004379.1	Q01459
	SPATA1	NM_001397487.1	MANE Select	c.1295-2477C>G		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.830G>C	p.Arg277Pro	missense	Exon 6 of 7	ENSP00000359664.4	Q01459
	SPATA1	ENST00000699524.1	MANE Select	c.1295-2477C>G		intron	N/A	ENSP00000514414.1	A0A8V8TNU4
	CTBS	ENST00000477677.5	TSL:1	n.686G>C		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1422726 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 708080

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31174

American (AMR) AF: 0.00 AC: 0 AN: 37640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24990

East Asian (EAS) AF: 0.00 AC: 0 AN: 37404

South Asian (SAS) AF: 0.00 AC: 0 AN: 80126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094798

Other (OTH) AF: 0.0000171 AC: 1 AN: 58434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.26
Sift	Benign	0.068	T
Sift4G	Uncertain	0.053	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.60		Loss of methylation at R277 (P = 0.0284)
MVP		0.53
MPC		0.43
ClinPred		0.99	D
GERP RS		0.97
Varity_R		0.57
gMVP		0.90
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs148118320; hg19: chr1-85029067;