Variant rs28941786 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001902.6(CTH):c.718C>G(p.Gln240Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,393,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CTH
NM_001902.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57

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 links:

CTH (HGNC:):

CTH links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

PP5

Variant 1-70430388-C-G is Pathogenic according to our data. Variant chr1-70430388-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2940.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTH	NM_001902.6 linkuse as main transcript	c.718C>G	p.Gln240Glu	missense_variant	7/12	ENST00000370938.8	NP_001893.2	P32929-1
CTH	NM_001190463.2 linkuse as main transcript	c.622C>G	p.Gln208Glu	missense_variant	6/11		NP_001177392.1	P32929-3
CTH	NM_153742.5 linkuse as main transcript	c.586C>G	p.Gln196Glu	missense_variant	6/11		NP_714964.2	P32929-2
CTH	XM_017000416.3 linkuse as main transcript	c.148C>G	p.Gln50Glu	missense_variant	4/9		XP_016855905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTH	ENST00000370938.8 linkuse as main transcript	c.718C>G	p.Gln240Glu	missense_variant	7/12	1	NM_001902.6	ENSP00000359976.3	P32929-1
CTH	ENST00000346806.2 linkuse as main transcript	c.586C>G	p.Gln196Glu	missense_variant	6/11	1		ENSP00000311554.2	P32929-2
CTH	ENST00000411986.6 linkuse as main transcript	c.622C>G	p.Gln208Glu	missense_variant	6/11	2		ENSP00000413407.2	P32929-3
CTH	ENST00000464926.1 linkuse as main transcript	n.766C>G		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251346

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1393214

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697500

show subpopulations

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:

0.00000381

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cystathioninuria

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

.;D;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.098

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.40

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.94

MutPred

0.87

.;Gain of methylation at R237 (P = 0.0747);.;

MVP

0.95

MPC

0.49

ClinPred

0.97

GERP RS

5.5

Varity_R

0.96

gMVP

0.87

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