1-84563354-C-T

Variant names:

• chr1-84563354-C-T
• rs375887489
• NM_004388.3:c.860G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_004388.3(CTBS):​c.860G>A​(p.Arg287His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,594,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R287C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CTBS NM_004388.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.84

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07396847).
• BP6: Variant 1-84563354-C-T is Benign according to our data. Variant chr1-84563354-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3498096.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3	c.860G>A	p.Arg287His	missense_variant	Exon 6 of 7	ENST00000370630.6	NP_004379.1
SPATA1	NM_001397487.1	c.1295-2507C>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.860G>A	p.Arg287His	missense_variant	Exon 6 of 7	1	NM_004388.3	ENSP00000359664.4
SPATA1	ENST00000699524.1	c.1295-2507C>T		intron_variant	Intron 13 of 13		NM_001397487.1	ENSP00000514414.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000114 AC: 27 AN: 235924 Hom.: 0 AF XY: 0.000117 AC XY: 15 AN XY: 128550

Gnomad AFR exome AF: 0.000138

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: 0.000221

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000115 AC: 166 AN: 1442774 Hom.: 0 Cov.: 30 AF XY: 0.000124 AC XY: 89 AN XY: 718110

Gnomad4 AFR exome AF: 0.000124

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.000101

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74284

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000107 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 29, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.32
DANN	Benign	0.91
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.055
Sift	Benign	0.31	T
Sift4G	Benign	0.33	T
Polyphen		0.10	B
Vest4		0.045
MVP		0.12
MPC		0.075
ClinPred		0.023	T
GERP RS		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs375887489; hg19: chr1-85029037; COSMIC: COSV55364512;