10-97590194-G-T

Variant names:

• chr10-97590194-G-T
• NM_001009997.3:c.297G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009997.3(C10orf62):​c.297G>T​(p.Lys99Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C10orf62 NM_001009997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

C10orf62 (HGNC:23294): (chromosome 10 open reading frame 62)

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]

ENSG00000249967 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14298892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C10orf62	NM_001009997.3	c.297G>T	p.Lys99Asn	missense_variant	Exon 1 of 1	ENST00000370640.5	NP_001009997.2
HOGA1	NM_138413.4	c.211+5280G>T		intron_variant	Intron 1 of 6	ENST00000370646.9	NP_612422.2
HOGA1	NM_001134670.2	c.211+5280G>T		intron_variant	Intron 1 of 2		NP_001128142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C10orf62	ENST00000370640.5	c.297G>T	p.Lys99Asn	missense_variant	Exon 1 of 1	6	NM_001009997.3	ENSP00000359674.3
HOGA1	ENST00000370646.9	c.211+5280G>T		intron_variant	Intron 1 of 6	1	NM_138413.4	ENSP00000359680.4
ENSG00000249967	ENST00000370649.3	c.211+5280G>T		intron_variant	Intron 1 of 9	2		ENSP00000359683.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.029	D
Sift4G	Benign	0.078	T
Polyphen		0.90	P
Vest4		0.056
MutPred		0.13		Loss of ubiquitination at K99 (P = 0.002);
MVP		0.75
MPC		0.15
ClinPred		0.37	T
GERP RS		3.8
Varity_R		0.20
gMVP		0.011

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-99349951;