Variant 2-42769679-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012205.3(HAAO):c.630+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,568,890 control chromosomes in the GnomAD database, including 12,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 896 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11569 hom. )

Consequence

HAAO
NM_012205.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.476

Variant links:

Genes affected

HAAO (HGNC:4796): (3-hydroxyanthranilate 3,4-dioxygenase) 3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]

HAAO links:

HAAO (HGNC:):

HAAO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-42769679-G-A is Benign according to our data. Variant chr2-42769679-G-A is described in ClinVar as [Benign]. Clinvar id is 1285319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HAAO	NM_012205.3 linkuse as main transcript	c.630+34C>T	intron_variant	ENST00000294973.11	NP_036337.2	P46952-1
HAAO	XM_011532729.4 linkuse as main transcript	c.540+34C>T	intron_variant		XP_011531031.1
HAAO	XM_011532730.4 linkuse as main transcript	c.528+34C>T	intron_variant		XP_011531032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAAO	ENST00000294973.11 linkuse as main transcript	c.630+34C>T		intron_variant		1	NM_012205.3	ENSP00000294973.6		P46952-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15376

AN:

151982

Hom.:

895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0854

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.108

AC:

23217

AN:

215942

Hom.:

1441

AF XY:

0.113

AC XY:

13049

AN XY:

115872

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.0624

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0237

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.124

AC:

175837

AN:

1416790

Hom.:

11569

Cov.:

AF XY:

0.125

AC XY:

87722

AN XY:

700500

show subpopulations

Gnomad4 AFR exome

AF:

0.0530

Gnomad4 AMR exome

AF:

0.0675

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.0144

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.101

AC:

15383

AN:

152100

Hom.:

896

Cov.:

AF XY:

0.100

AC XY:

7472

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0519

Gnomad4 AMR

AF:

0.0852

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.114

Hom.:

447

Bravo

AF:

0.0949

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Vertebral, cardiac, renal, and limb defects syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.87

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