rs386833596

Variant names:

• chr10-124398090-C-A
• NM_000274.4:c.1172G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-124398090-C-A
• chr10-124398090-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000274.4(OAT):​c.1172G>T​(p.Trp391Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OAT NM_000274.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

Genes affected

OAT (HGNC:8091): (ornithine aminotransferase) This gene encodes the mitochondrial enzyme ornithine aminotransferase, which is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Mutations that result in a deficiency of this enzyme cause the autosomal recessive eye disease Gyrate Atrophy. Alternatively spliced transcript variants encoding different isoforms have been described. Related pseudogenes have been defined on the X chromosome. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a helix (size 9) in uniprot entity OAT_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000274.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAT	NM_000274.4	c.1172G>T	p.Trp391Leu	missense_variant	Exon 10 of 10	ENST00000368845.6	NP_000265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAT	ENST00000368845.6	c.1172G>T	p.Trp391Leu	missense_variant	Exon 10 of 10	1	NM_000274.4	ENSP00000357838.5
OAT	ENST00000539214.5	c.758G>T	p.Trp253Leu	missense_variant	Exon 9 of 9	1		ENSP00000439042.1
OAT	ENST00000471127.1	n.682G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Pathogenic	0.90	.;D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-9.1	D;D
REVEL	Uncertain	0.58
Sift	Benign	0.033	D;D
Sift4G	Benign	0.50	T;T
Polyphen		0.0090	.;B
Vest4		0.62
MutPred		0.54		.;Gain of methylation at R396 (P = 0.0401);
MVP		0.97
MPC		0.68
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-126086659;