Variant 12-121856304-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000289004.8(HPD):c.324+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,604,710 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

HPD
ENST00000289004.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.265

Variant links:

Genes affected

HPD (HGNC:5147): (4-hydroxyphenylpyruvate dioxygenase) The protein encoded by this gene is an enzyme in the catabolic pathway of tyrosine. The encoded protein catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. Defects in this gene are a cause of tyrosinemia type 3 (TYRO3) and hawkinsinuria (HAWK). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

HPD links:

ENSG00000256811 (HGNC:):

ENSG00000256811 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-121856304-C-T is Benign according to our data. Variant chr12-121856304-C-T is described in ClinVar as [Benign]. Clinvar id is 1166574.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
HPD	NM_002150.3 linkuse as main transcript	c.324+20G>A	intron_variant		ENST00000289004.8	NP_002141.2	P32754
HPD	NM_001171993.2 linkuse as main transcript	c.207+20G>A	intron_variant			NP_001165464.1	P32754-2
LOC105370035	XR_002957437.2 linkuse as main transcript	n.52C>T	non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HPD	ENST00000289004.8 linkuse as main transcript	c.324+20G>A	intron_variant		1	NM_002150.3	ENSP00000289004.4	A0A0B4J1R4
HPD	ENST00000543163.5 linkuse as main transcript	c.207+20G>A	intron_variant		5		ENSP00000441677.1	P32754-2
ENSG00000256811	ENST00000543848.1 linkuse as main transcript	n.46C>T	non_coding_transcript_exon_variant	1/3	3
HPD	ENST00000542159.2 linkuse as main transcript	n.360+20G>A	intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

306

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00666

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000620

AC:

156

AN:

251426

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00757

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000196

AC:

284

AN:

1452400

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

112

AN XY:

723194

show subpopulations

Gnomad4 AFR exome

AF:

0.00654

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.000483

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152310

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00669

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tyrosinemia type III;C2931042:Hawkinsinuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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