NM_001902.6:c.346+125A>T

Variant names:

• chr1-70418157-A-T
• rs1145920
• NM_001902.6:c.346+125A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001902.6(CTH):​c.346+125A>T variant causes a intron 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 14 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: ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	NM_001902.6	MANE Select	c.346+125A>T		intron	N/A	NP_001893.2
	CTH	NM_001190463.2		c.250+2120A>T		intron	N/A	NP_001177392.1
	CTH	NM_153742.5		c.346+125A>T		intron	N/A	NP_714964.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	ENST00000370938.8	TSL:1 MANE Select	c.346+125A>T		intron	N/A	ENSP00000359976.3
	CTH	ENST00000346806.2	TSL:1	c.346+125A>T		intron	N/A	ENSP00000311554.2
	CTH	ENST00000411986.6	TSL:2	c.250+2120A>T		intron	N/A	ENSP00000413407.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1007098 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 512940

African (AFR) AF: 0.00 AC: 0 AN: 23598

American (AMR) AF: 0.00 AC: 0 AN: 34430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22270

East Asian (EAS) AF: 0.00 AC: 0 AN: 33698

South Asian (SAS) AF: 0.00 AC: 0 AN: 69786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 733318

Other (OTH) AF: 0.00 AC: 0 AN: 45068

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 143009

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.018
DANN	Benign	0.65
PhyloP100		-2.5

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

Other links and lift over

dbSNP: rs1145920; hg19: chr1-70883840;