Genetic Variant CTBS:p.Ile271Thr (chr1-84563402-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004388.3(CTBS):c.812T>C(p.Ile271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,571,834 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 14 hom. )

Consequence

CTBS
NM_004388.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.13

Variant links:

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]

CTBS links:

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

SPATA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054585338).

BP6

Variant 1-84563402-A-G is Benign according to our data. Variant chr1-84563402-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638903.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3 link	c.812T>C	p.Ile271Thr	missense_variant	Exon 6 of 7	ENST00000370630.6	NP_004379.1	Q01459Q8TC97
SPATA1	NM_001397487.1 link	c.1295-2459A>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 link	c.812T>C	p.Ile271Thr	missense_variant	Exon 6 of 7	1	NM_004388.3	ENSP00000359664.4		Q01459
SPATA1	ENST00000699524.1 link	c.1295-2459A>G		intron_variant	Intron 13 of 13		NM_001397487.1	ENSP00000514414.1		A0A8V8TNU4

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00495

AC:

1072

AN:

216422

Hom.:

AF XY:

0.00492

AC XY:

584

AN XY:

118662

show subpopulations

Gnomad AFR exome

AF:

0.000746

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00443

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00237

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.00420

Gnomad OTH exome

AF:

0.00590

GnomAD4 exome

AF:

0.00337

AC:

4787

AN:

1419580

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

2382

AN XY:

706266

show subpopulations

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.00465

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00279

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.00286

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00426

AC:

648

AN:

152254

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00408

AC:

495

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CTBS: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.11

Sift

Benign

0.066

Sift4G

Benign

0.091

Polyphen

0.63

Vest4

0.10

MVP

0.50

MPC

0.20

ClinPred

0.035

GERP RS

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over