1-70432153-A-C

Variant names:

• chr1-70432153-A-C
• NM_001902.6:c.795A>C
• CTH p.Arg265Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001902.6(CTH):​c.795A>C​(p.Arg265Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTH NM_001902.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 0 publications found

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

ENSG00000306600 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.278 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	NM_001902.6	MANE Select	c.795A>C	p.Arg265Arg	synonymous	Exon 8 of 12	NP_001893.2
	CTH	NM_001190463.2		c.699A>C	p.Arg233Arg	synonymous	Exon 7 of 11	NP_001177392.1	P32929-3
	CTH	NM_153742.5		c.663A>C	p.Arg221Arg	synonymous	Exon 7 of 11	NP_714964.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	ENST00000370938.8	TSL:1 MANE Select	c.795A>C	p.Arg265Arg	synonymous	Exon 8 of 12	ENSP00000359976.3	P32929-1
	CTH	ENST00000346806.2	TSL:1	c.663A>C	p.Arg221Arg	synonymous	Exon 7 of 11	ENSP00000311554.2	P32929-2
	CTH	ENST00000896200.1		c.795A>C	p.Arg265Arg	synonymous	Exon 9 of 13	ENSP00000566259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.58
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-70897836;