rs12261752

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_138413.4(HOGA1):c.912C>A(p.Ala304Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,966 control chromosomes in the GnomAD database, including 76,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7081 hom., cov: 33)

Exomes 𝑓: 0.30 ( 69495 hom. )

Consequence

HOGA1
NM_138413.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:11

Conservation

PhyloP100: -0.248

Publications

14 publications found

Variant links:

Genes affected

HOGA1 (HGNC:25155): (4-hydroxy-2-oxoglutarate aldolase 1) The authors of PMID:20797690 cloned this gene while searching for genes in a region of chromosome 10 linked to primary hyperoxalurea type III. They noted that even though the encoded protein has been described as a mitochondrial dihydrodipicolinate synthase-like enzyme, it shares little homology with E. coli dihydrodipicolinate synthase (Dhdps), particularly in the putative substrate-binding region. Moreover, neither lysine biosynthesis nor sialic acid metabolism, for which Dhdps is responsible, occurs in vertebrate mitochondria. They propose that this gene encodes mitochondrial 4-hydroxyl-2-oxoglutarate aldolase (EC 4.1.3.16), which catalyzes the final step in the metabolic pathway of hydroxyproline, releasing glyoxylate and pyruvate. This gene is predominantly expressed in the liver and kidney, and mutations in this gene are found in patients with primary hyperoxalurea type III. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2010]

HOGA1 Gene-Disease associations (from GenCC):

primary hyperoxaluria type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

HOGA1 links:

ENSG00000249967 (HGNC:):

ENSG00000249967 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 10-97611587-C-A is Benign according to our data. Variant chr10-97611587-C-A is described in ClinVar as Benign. ClinVar VariationId is 204264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOGA1	NM_138413.4	MANE Select	c.912C>A	p.Ala304Ala	synonymous	Exon 7 of 7	NP_612422.2
	HOGA1	NM_001134670.2		c.423C>A	p.Ala141Ala	synonymous	Exon 3 of 3	NP_001128142.1	Q86XE5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOGA1	ENST00000370646.9	TSL:1 MANE Select	c.912C>A	p.Ala304Ala	synonymous	Exon 7 of 7	ENSP00000359680.4	Q86XE5-1
HOGA1	ENST00000370647.8	TSL:1	c.423C>A	p.Ala141Ala	synonymous	Exon 3 of 3	ENSP00000359681.4	Q86XE5-3
ENSG00000249967	ENST00000370649.3	TSL:2	c.345+9597C>A		intron	N/A	ENSP00000359683.3	E9PAM4

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45792

AN:

152082

Hom.:

7064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.301

AC:

75578

AN:

251064

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.305

AC:

445215

AN:

1461766

Hom.:

69495

Cov.:

AF XY:

0.308

AC XY:

224023

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.315

AC:

10558

AN:

33478

American (AMR)

AF:

0.217

AC:

9694

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9139

AN:

26136

East Asian (EAS)

AF:

0.418

AC:

16589

AN:

39698

South Asian (SAS)

AF:

0.397

AC:

34241

AN:

86254

European-Finnish (FIN)

AF:

0.255

AC:

13622

AN:

53366

Middle Eastern (MID)

AF:

0.320

AC:

1848

AN:

5768

European-Non Finnish (NFE)

AF:

0.297

AC:

330210

AN:

1111954

Other (OTH)

AF:

0.320

AC:

19314

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

18218

36436

54653

72871

91089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11042

22084

33126

44168

55210

<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:

0.301

AC:

45842

AN:

152200

Hom.:

7081

Cov.:

AF XY:

0.299

AC XY:

22234

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.307

AC:

12755

AN:

41530

American (AMR)

AF:

0.257

AC:

3937

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1235

AN:

3472

East Asian (EAS)

AF:

0.377

AC:

1945

AN:

5166

South Asian (SAS)

AF:

0.396

AC:

1909

AN:

4826

European-Finnish (FIN)

AF:

0.241

AC:

2556

AN:

10606

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20415

AN:

67990

Other (OTH)

AF:

0.302

AC:

638

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1695

3390

5084

6779

8474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.301

Hom.:

5641

Bravo

AF:

0.302

Asia WGS

AF:

0.403

AC:

1400

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.291

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary hyperoxaluria type 3 (5)

not specified (4)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

7.8

(source)

DANN

Benign

0.77

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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