dbSNP rs3842726: ENSG00000295384:n.175-3914C>G (chr11-2163897-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000729705.1(ENSG00000295384):n.175-3914C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 209,268 control chromosomes in the GnomAD database, including 1,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 1505 hom., cov: 33)

Exomes 𝑓: 0.014 ( 101 hom. )

Consequence

ENSG00000295384
ENST00000729705.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.459

Publications

3 publications found

Variant links:

Genes affected

ENSG00000295384 (HGNC:):

ENSG00000295384 links:

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 Gene-Disease associations (from GenCC):

TH-deficient dopa-responsive dystonia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
tyrosine hydroxylase deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women's Health

TH links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000729705.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-2163897-C-G is Benign according to our data. Variant chr11-2163897-C-G is described in ClinVar as Benign. ClinVar VariationId is 1274135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000729705.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TH	NM_000360.4	MANE Select	c.*336G>C	downstream_gene	N/A	NP_000351.2	P07101-3
TH	NM_199292.3		c.*336G>C	downstream_gene	N/A	NP_954986.2	P07101-1
TH	NM_199293.3		c.*336G>C	downstream_gene	N/A	NP_954987.2	P07101-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000295384	ENST00000729705.1		n.175-3914C>G	intron	N/A
ENSG00000295384	ENST00000729706.1		n.226-3914C>G	intron	N/A
TH	ENST00000352909.8	TSL:1 MANE Select	c.*336G>C	downstream_gene	N/A	ENSP00000325951.4	P07101-3

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11841

AN:

152090

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.0549

GnomAD4 exome

AF:

0.0137

AC:

779

AN:

57060

Hom.:

101

Cov.:

AF XY:

0.0122

AC XY:

351

AN XY:

28656

show subpopulations

African (AFR)

AF:

0.269

AC:

576

AN:

2140

American (AMR)

AF:

0.0232

AC:

AN:

1552

Ashkenazi Jewish (ASJ)

AF:

0.00491

AC:

AN:

2446

East Asian (EAS)

AF:

0.00

AC:

AN:

4934

South Asian (SAS)

AF:

0.00

AC:

AN:

550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3424

Middle Eastern (MID)

AF:

0.0222

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00120

AC:

AN:

37514

Other (OTH)

AF:

0.0246

AC:

103

AN:

4184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0780

AC:

11873

AN:

152208

Hom.:

1505

Cov.:

AF XY:

0.0751

AC XY:

5589

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.267

AC:

11088

AN:

41494

American (AMR)

AF:

0.0348

AC:

533

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00147

AC:

100

AN:

67996

Other (OTH)

AF:

0.0543

AC:

115

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

466

933

1399

1866

2332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0610

Hom.:

126

Bravo

AF:

0.0900

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.49

PhyloP100

-0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over