1-84563387-A-G

Variant names:

• chr1-84563387-A-G
• rs1161357596
• NM_004388.3:c.827T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004388.3(CTBS):​c.827T>C​(p.Phe276Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CTBS NM_004388.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2967139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3	c.827T>C	p.Phe276Ser	missense_variant	Exon 6 of 7	ENST00000370630.6	NP_004379.1
SPATA1	NM_001397487.1	c.1295-2474A>G		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.827T>C	p.Phe276Ser	missense_variant	Exon 6 of 7	1	NM_004388.3	ENSP00000359664.4
SPATA1	ENST00000699524.1	c.1295-2474A>G		intron_variant	Intron 13 of 13		NM_001397487.1	ENSP00000514414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424984 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709178

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.827T>C (p.F276S) alteration is located in exon 6 (coding exon 6) of the CTBS gene. This alteration results from a T to C substitution at nucleotide position 827, causing the phenylalanine (F) at amino acid position 276 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	0.73
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.0022
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.17
Sift	Benign	0.065	T
Sift4G	Benign	0.063	T
Polyphen		0.49	P
Vest4		0.29
MVP		0.46
MPC		0.25
ClinPred		0.96	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.88

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

Other links and lift over

dbSNP: rs1161357596; hg19: chr1-85029070;