rs149580405
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000360.4(TH):c.153G>A(p.Ala51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,611,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
TH
NM_000360.4 synonymous
NM_000360.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.40
Genes affected
TH (HGNC:11782): (tyrosine hydroxylase) The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 11-2169809-C-T is Benign according to our data. Variant chr11-2169809-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 455994.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.4 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TH | NM_000360.4 | c.153G>A | p.Ala51= | synonymous_variant | 2/13 | ENST00000352909.8 | |
TH | NM_199292.3 | c.246G>A | p.Ala82= | synonymous_variant | 3/14 | ||
TH | NM_199293.3 | c.234G>A | p.Ala78= | synonymous_variant | 3/14 | ||
TH | XM_011520335.3 | c.165G>A | p.Ala55= | synonymous_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TH | ENST00000352909.8 | c.153G>A | p.Ala51= | synonymous_variant | 2/13 | 1 | NM_000360.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000208 AC: 5AN: 240060Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131678
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1458938Hom.: 0 Cov.: 37 AF XY: 0.00000689 AC XY: 5AN XY: 725738
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive DOPA responsive dystonia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 17, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at