chr10-97599982-T-C

Variant names:

• chr10-97599982-T-C
• rs2297644
• NM_138413.4:c.604-85T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138413.4(HOGA1):​c.604-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,485,160 control chromosomes in the GnomAD database, including 19,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1852 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17530 hom.)
• Consequence: HOGA1 NM_138413.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26
• Publications: 16 publications found

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: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000249967 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-97599982-T-C is Benign according to our data. Variant chr10-97599982-T-C is described in ClinVar as Benign. ClinVar VariationId is 1234774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOGA1	NM_138413.4	c.604-85T>C		intron_variant	Intron 4 of 6	ENST00000370646.9	NP_612422.2
HOGA1	NM_001134670.2	c.212-1875T>C		intron_variant	Intron 1 of 2		NP_001128142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOGA1	ENST00000370646.9	c.604-85T>C		intron_variant	Intron 4 of 6	1	NM_138413.4	ENSP00000359680.4
ENSG00000249967	ENST00000370649.3	c.212-1875T>C		intron_variant	Intron 1 of 9	2		ENSP00000359683.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22854 AN: 152038 Hom.: 1851 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.156 AC: 208212 AN: 1333004 Hom.: 17530 Cov.: 21 AF XY: 0.155 AC XY: 103693 AN XY: 670016

African (AFR) AF: 0.149 AC: 4574 AN: 30796

American (AMR) AF: 0.0671 AC: 2989 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3080 AN: 25392

East Asian (EAS) AF: 0.0544 AC: 2127 AN: 39132

South Asian (SAS) AF: 0.107 AC: 8947 AN: 83592

European-Finnish (FIN) AF: 0.188 AC: 10026 AN: 53302

Middle Eastern (MID) AF: 0.0899 AC: 495 AN: 5508

European-Non Finnish (NFE) AF: 0.169 AC: 167754 AN: 994506

Other (OTH) AF: 0.146 AC: 8220 AN: 56218

GnomAD4 genome AF: 0.150 AC: 22862 AN: 152156 Hom.: 1852 Cov.: 32 AF XY: 0.148 AC XY: 11025 AN XY: 74386

African (AFR) AF: 0.147 AC: 6112 AN: 41506

American (AMR) AF: 0.0920 AC: 1406 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.0538 AC: 279 AN: 5184

South Asian (SAS) AF: 0.104 AC: 499 AN: 4812

European-Finnish (FIN) AF: 0.185 AC: 1959 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11818 AN: 68008

Other (OTH) AF: 0.123 AC: 258 AN: 2106

Alfa AF: 0.162 Hom.: 6783

Bravo AF: 0.141

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-1.3
PromoterAI		-0.027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2297644; hg19: chr10-99359739; COSMIC: COSV65706236;