Genetic Variant CTBS:p.Arg349Trp (chr1-84555112-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004388.3(CTBS):c.1045C>T(p.Arg349Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,736 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R349Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00072 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 45 hom. )

Consequence

CTBS
NM_004388.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.35

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:

ENSG00000285851 (HGNC:):

ENSG00000285851 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014495879).

BP6

Variant 1-84555112-G-A is Benign according to our data. Variant chr1-84555112-G-A is described in ClinVar as [Benign]. Clinvar id is 723110.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000723 (110/152126) while in subpopulation SAS AF= 0.0216 (104/4818). AF 95% confidence interval is 0.0182. There are 4 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBS	NM_004388.3 link	c.1045C>T	p.Arg349Trp	missense_variant	Exon 7 of 7	ENST00000370630.6	NP_004379.1	Q01459Q8TC97
SPATA1	NM_001397487.1 link	c.1225-798G>A		intron_variant	Intron 12 of 13	ENST00000699524.1	NP_001384416.1
SPATA1	NM_001310156.2 link	c.*1-798G>A		intron_variant	Intron 13 of 13		NP_001297085.2	Q5VX52
SPATA1	XM_011542514.3 link	c.*1-798G>A		intron_variant	Intron 12 of 12		XP_011540816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBS	ENST00000370630.6 link	c.1045C>T	p.Arg349Trp	missense_variant	Exon 7 of 7	1	NM_004388.3	ENSP00000359664.4		Q01459
SPATA1	ENST00000699524.1 link	c.1225-798G>A		intron_variant	Intron 12 of 13		NM_001397487.1	ENSP00000514414.1		A0A8V8TNU4

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

110

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00242

AC:

608

AN:

251372

Hom.:

AF XY:

0.00332

AC XY:

451

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0193

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00119

AC:

1740

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1250

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152126

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00277

AC:

336

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 27, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.33

MVP

0.70

MPC

0.38

ClinPred

0.15

GERP RS

3.5

Varity_R

0.43

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