rs3842724
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000360.4(TH):c.1401C>T(p.Asp467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,540,704 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 128 hom., cov: 33)
Exomes 𝑓: 0.0029 ( 110 hom. )
Consequence
TH
NM_000360.4 synonymous
NM_000360.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.16
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 11-2164326-G-A is Benign according to our data. Variant chr11-2164326-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 304066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.15 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TH | NM_000360.4 | c.1401C>T | p.Asp467= | synonymous_variant | 13/13 | ENST00000352909.8 | |
TH | NM_199292.3 | c.1494C>T | p.Asp498= | synonymous_variant | 14/14 | ||
TH | NM_199293.3 | c.1482C>T | p.Asp494= | synonymous_variant | 14/14 | ||
TH | XM_011520335.3 | c.1413C>T | p.Asp471= | synonymous_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TH | ENST00000352909.8 | c.1401C>T | p.Asp467= | synonymous_variant | 13/13 | 1 | NM_000360.4 | P1 | |
TH | ENST00000381178.5 | c.1494C>T | p.Asp498= | synonymous_variant | 14/14 | 1 | |||
TH | ENST00000381175.5 | c.1482C>T | p.Asp494= | synonymous_variant | 14/14 | 1 | |||
TH | ENST00000333684.9 | c.1119C>T | p.Asp373= | synonymous_variant | 11/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0242 AC: 3680AN: 152210Hom.: 128 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
3680
AN:
152210
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00690 AC: 1374AN: 199126Hom.: 55 AF XY: 0.00513 AC XY: 553AN XY: 107776
GnomAD3 exomes
AF:
AC:
1374
AN:
199126
Hom.:
AF XY:
AC XY:
553
AN XY:
107776
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00287 AC: 3982AN: 1388376Hom.: 110 Cov.: 31 AF XY: 0.00264 AC XY: 1802AN XY: 683680
GnomAD4 exome
AF:
AC:
3982
AN:
1388376
Hom.:
Cov.:
31
AF XY:
AC XY:
1802
AN XY:
683680
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0242 AC: 3681AN: 152328Hom.: 128 Cov.: 33 AF XY: 0.0231 AC XY: 1717AN XY: 74480
GnomAD4 genome
?
AF:
AC:
3681
AN:
152328
Hom.:
Cov.:
33
AF XY:
AC XY:
1717
AN XY:
74480
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
14
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive DOPA responsive dystonia Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 12, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2018 | - - |
Transient Neonatal Diabetes, Dominant/Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Maturity onset diabetes mellitus in young Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at