rs1480544

Positions:

• chr4-170066485-A-G
• chr4-170066485-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016228.4(AADAT):​c.963-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,607,470 control chromosomes in the GnomAD database, including 232,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (30620 hom., cov: 32)
  • Exomes 𝑓: 0.51 (201698 hom.)
• Consequence: AADAT NM_016228.4 splice_region, intron
• Scores: Splicing: ADA: 0.00007596
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859

Genes affected

AADAT (HGNC:17929): (aminoadipate aminotransferase) This gene encodes a protein that is highly similar to mouse and rat kynurenine aminotransferase II. The rat protein is a homodimer with two transaminase activities. One activity is the transamination of alpha-aminoadipic acid, a final step in the saccaropine pathway which is the major pathway for L-lysine catabolism. The other activity involves the transamination of kynurenine to produce kynurenine acid, the precursor of kynurenic acid which has neuroprotective properties. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

LOC107986326 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADAT	NM_016228.4	c.963-7T>C		splice_region_variant, intron_variant		ENST00000337664.9	NP_057312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADAT	ENST00000337664.9	c.963-7T>C		splice_region_variant, intron_variant		1	NM_016228.4	ENSP00000336808.4
AADAT	ENST00000509167.5	c.975-7T>C		splice_region_variant, intron_variant		1		ENSP00000423190.1
AADAT	ENST00000515480.5	c.963-7T>C		splice_region_variant, intron_variant		1		ENSP00000423341.1
AADAT	ENST00000353187.6	c.963-7T>C		splice_region_variant, intron_variant		2		ENSP00000226840.4

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92591 AN: 151948 Hom.: 30568 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.595

GnomAD3 exomes AF: 0.572 AC: 143130 AN: 250396 Hom.: 43990 AF XY: 0.568 AC XY: 76944 AN XY: 135350

Gnomad AFR exome AF: 0.853

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.981

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.514 AC: 748446 AN: 1455402 Hom.: 201698 Cov.: 31 AF XY: 0.518 AC XY: 375042 AN XY: 724278

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.977

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.610 AC: 92693 AN: 152068 Hom.: 30620 Cov.: 32 AF XY: 0.610 AC XY: 45360 AN XY: 74346

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.600

Alfa AF: 0.467 Hom.: 4828

Bravo AF: 0.631

Asia WGS AF: 0.829 AC: 2880 AN: 3478

EpiCase AF: 0.495

EpiControl AF: 0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.0060
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

LitVar

Other links and lift over

dbSNP: rs1480544; hg19: chr4-170987636;