rs3842724

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.Asp467Asp) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.16

Variant links:

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]

TH links:

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 rank	MANE	Protein	UniProt
TH	NM_000360.4 link	c.1401C>T	p.Asp467Asp	synonymous_variant	Exon 13 of 13	ENST00000352909.8	NP_000351.2	P07101-3
TH	NM_199292.3 link	c.1494C>T	p.Asp498Asp	synonymous_variant	Exon 14 of 14		NP_954986.2	P07101-1P78428
TH	NM_199293.3 link	c.1482C>T	p.Asp494Asp	synonymous_variant	Exon 14 of 14		NP_954987.2	P07101-2P78428
TH	XM_011520335.3 link	c.1413C>T	p.Asp471Asp	synonymous_variant	Exon 13 of 13		XP_011518637.1	P07101-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TH	ENST00000352909.8 link	c.1401C>T	p.Asp467Asp	synonymous_variant	Exon 13 of 13	1	NM_000360.4	ENSP00000325951.4	P07101-3
TH	ENST00000381178.5 link	c.1494C>T	p.Asp498Asp	synonymous_variant	Exon 14 of 14	1		ENSP00000370571.1	P07101-1
TH	ENST00000381175.5 link	c.1482C>T	p.Asp494Asp	synonymous_variant	Exon 14 of 14	1		ENSP00000370567.1	P07101-2
TH	ENST00000333684.9 link	c.1119C>T	p.Asp373Asp	synonymous_variant	Exon 11 of 11	1		ENSP00000328814.6	P07101-6

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3680

AN:

152210

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00690

AC:

1374

AN:

199126

Hom.:

AF XY:

0.00513

AC XY:

553

AN XY:

107776

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.00493

Gnomad ASJ exome

AF:

0.00314

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000182

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000763

Gnomad OTH exome

AF:

0.00498

GnomAD4 exome

AF:

0.00287

AC:

3982

AN:

1388376

Hom.:

110

Cov.:

AF XY:

0.00264

AC XY:

1802

AN XY:

683680

show subpopulations

Gnomad4 AFR exome

AF:

0.0779

Gnomad4 AMR exome

AF:

0.00593

Gnomad4 ASJ exome

AF:

0.00339

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000825

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.0242

AC:

3681

AN:

152328

Hom.:

128

Cov.:

AF XY:

0.0231

AC XY:

1717

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0795

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0278

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive DOPA responsive dystonia

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Transient Neonatal Diabetes, Dominant/Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Maturity onset diabetes mellitus in young

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.43

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over