chr1-70424340-G-A

Variant names:

• chr1-70424340-G-A
• NM_001902.6:c.512G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001902.6(CTH):​c.512G>A​(p.Gly171Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G171A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTH NM_001902.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTH	NM_001902.6	c.512G>A	p.Gly171Asp	missense_variant	Exon 5 of 12	ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.416G>A	p.Gly139Asp	missense_variant	Exon 4 of 11		NP_001177392.1
CTH	XM_017000416.3	c.-59G>A		5_prime_UTR_variant	Exon 2 of 9		XP_016855905.1
CTH	NM_153742.5	c.456+2665G>A		intron_variant	Intron 4 of 10		NP_714964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.512G>A	p.Gly171Asp	missense_variant	Exon 5 of 12	1	NM_001902.6	ENSP00000359976.3
CTH	ENST00000346806.2	c.456+2665G>A		intron_variant	Intron 4 of 10	1		ENSP00000311554.2
CTH	ENST00000411986.6	c.416G>A	p.Gly139Asp	missense_variant	Exon 4 of 11	2		ENSP00000413407.2
CTH	ENST00000464926.1	n.560G>A		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;D
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.21	.;B
Vest4		0.52
MutPred		0.61		.;Gain of sheet (P = 0.1945);
MVP		0.81
MPC		0.24
ClinPred		0.64	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-70890023;