rs1021737

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001902.6(CTH):c.1208G>T(p.Ser403Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,608,522 control chromosomes in the GnomAD database, including 66,116 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4981 hom., cov: 31)

Exomes 𝑓: 0.28 ( 61135 hom. )

Consequence

CTH
NM_001902.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.0840

Publications

65 publications found

Variant links:

Genes affected

CTH (HGNC:2501): (cystathionine gamma-lyase) This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine. Mutations in this gene cause cystathioninuria. Alternative splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

CTH Gene-Disease associations (from GenCC):

cystathioninuria
Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen

CTH links:

ENSG00000306600 (HGNC:):

ENSG00000306600 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.174313E-4).

BP6

Variant 1-70439117-G-T is Benign according to our data. Variant chr1-70439117-G-T is described in ClinVar as Benign. ClinVar VariationId is 2941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001902.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTH	NM_001902.6	MANE Select	c.1208G>T	p.Ser403Ile	missense	Exon 12 of 12	NP_001893.2
CTH	NM_001190463.2		c.1112G>T	p.Ser371Ile	missense	Exon 11 of 11	NP_001177392.1	P32929-3
CTH	NM_153742.5		c.1076G>T	p.Ser359Ile	missense	Exon 11 of 11	NP_714964.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTH	ENST00000370938.8	TSL:1 MANE Select	c.1208G>T	p.Ser403Ile	missense	Exon 12 of 12	ENSP00000359976.3	P32929-1
CTH	ENST00000346806.2	TSL:1	c.1076G>T	p.Ser359Ile	missense	Exon 11 of 11	ENSP00000311554.2	P32929-2
CTH	ENST00000896200.1		c.1208G>T	p.Ser403Ile	missense	Exon 13 of 13	ENSP00000566259.1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36123

AN:

151884

Hom.:

4984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0994

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.285

AC:

71530

AN:

251056

AF XY:

0.282

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.284

AC:

414271

AN:

1456520

Hom.:

61135

Cov.:

AF XY:

0.283

AC XY:

204939

AN XY:

724830

show subpopulations

African (AFR)

AF:

0.0967

AC:

3232

AN:

33426

American (AMR)

AF:

0.422

AC:

18868

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

6941

AN:

26098

East Asian (EAS)

AF:

0.237

AC:

9402

AN:

39656

South Asian (SAS)

AF:

0.239

AC:

20591

AN:

86158

European-Finnish (FIN)

AF:

0.287

AC:

15329

AN:

53386

Middle Eastern (MID)

AF:

0.211

AC:

1214

AN:

5760

European-Non Finnish (NFE)

AF:

0.291

AC:

322380

AN:

1107136

Other (OTH)

AF:

0.271

AC:

16314

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

14010

28019

42029

56038

70048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10538

21076

31614

42152

52690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.238

AC:

36120

AN:

152002

Hom.:

4981

Cov.:

AF XY:

0.238

AC XY:

17677

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0993

AC:

4120

AN:

41492

American (AMR)

AF:

0.337

AC:

5140

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

949

AN:

3462

East Asian (EAS)

AF:

0.215

AC:

1111

AN:

5166

South Asian (SAS)

AF:

0.232

AC:

1117

AN:

4808

European-Finnish (FIN)

AF:

0.276

AC:

2910

AN:

10554

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19941

AN:

67946

Other (OTH)

AF:

0.228

AC:

480

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1346

2692

4039

5385

6731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.270

Hom.:

19918

Bravo

AF:

0.241

TwinsUK

AF:

0.297

AC:

1100

ALSPAC

AF:

0.276

AC:

1065

ESP6500AA

AF:

0.108

AC:

476

ESP6500EA

AF:

0.304

AC:

2617

ExAC

AF:

0.277

AC:

33636

Asia WGS

AF:

0.219

AC:

760

AN:

3478

EpiCase

AF:

0.276

EpiControl

AF:

0.280

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cystathioninuria (2)

CTH-related disorder (1)

not provided (1)

Homocysteine level elevated (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.026

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.56

MetaRNN

Benign

0.00072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.084

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.10

REVEL

Benign

0.12

Sift

Benign

0.065

Sift4G

Benign

0.12

Polyphen

0.23

Vest4

0.19

MPC

0.18

ClinPred

0.0026

GERP RS

0.84

Varity_R

0.049

gMVP

0.47

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over