rs201396618

Variant names:

• chr10-124411956-A-ATTAATT
• rs201396618
• NM_000274.4:c.199+11_199+16dupAATTAA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000274.4(OAT):​c.199+11_199+16dupAATTAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,610,558 control chromosomes in the GnomAD database, including 92 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (15 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (77 hom.)
• Consequence: OAT NM_000274.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.841
• Publications: 1 publications found

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]

OAT Gene-Disease associations (from GenCC):

• ornithine aminotransferase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-124411956-A-ATTAATT is Benign according to our data. Variant chr10-124411956-A-ATTAATT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 556600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00457 (696/152316) while in subpopulation EAS AF = 0.0179 (93/5194). AF 95% confidence interval is 0.015. There are 15 homozygotes in GnomAd4. There are 524 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000274.4. 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
	OAT	NM_000274.4	MANE Select	c.199+11_199+16dupAATTAA		intron	N/A	NP_000265.1	P04181-1
	OAT	NM_001322965.2		c.199+11_199+16dupAATTAA		intron	N/A	NP_001309894.1	P04181-1
	OAT	NM_001322966.2		c.199+11_199+16dupAATTAA		intron	N/A	NP_001309895.1	P04181-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	ENST00000368845.6	TSL:1 MANE Select	c.199+16_199+17insAATTAA		intron	N/A	ENSP00000357838.5	P04181-1
	OAT	ENST00000539214.5	TSL:1	c.-215-2992_-215-2991insAATTAA		intron	N/A	ENSP00000439042.1	P04181-2
	OAT	ENST00000921313.1		c.199+16_199+17insAATTAA		intron	N/A	ENSP00000591372.1

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 696 AN: 152198 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00683 AC: 1717 AN: 251420 AF XY: 0.00695

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0263

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00268 AC: 3903 AN: 1458242 Hom.: 77 Cov.: 32 AF XY: 0.00269 AC XY: 1949 AN XY: 725722

African (AFR) AF: 0.0000299 AC: 1 AN: 33416

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26112

East Asian (EAS) AF: 0.0258 AC: 1025 AN: 39668

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86164

European-Finnish (FIN) AF: 0.0446 AC: 2383 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.000237 AC: 263 AN: 1108700

Other (OTH) AF: 0.00285 AC: 172 AN: 60284

GnomAD4 genome AF: 0.00457 AC: 696 AN: 152316 Hom.: 15 Cov.: 33 AF XY: 0.00704 AC XY: 524 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5194

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00185 Hom.: 1

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ornithine aminotransferase deficiency (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs201396618; hg19: chr10-126100525;