NM_016228.4:c.963-7T>C

Variant names:

• chr4-170066485-A-G
• rs1480544
• NM_016228.4:c.963-7T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AADAT	NM_016228.4	c.963-7T>C		splice_region_variant, intron_variant	Intron 9 of 12	ENST00000337664.9	NP_057312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AADAT	ENST00000337664.9	c.963-7T>C		splice_region_variant, intron_variant	Intron 9 of 12	1	NM_016228.4	ENSP00000336808.4
AADAT	ENST00000509167.5	c.975-7T>C		splice_region_variant, intron_variant	Intron 10 of 13	1		ENSP00000423190.1
AADAT	ENST00000515480.5	c.963-7T>C		splice_region_variant, intron_variant	Intron 10 of 13	1		ENSP00000423341.1
AADAT	ENST00000353187.6	c.963-7T>C		splice_region_variant, intron_variant	Intron 10 of 13	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

GnomAD2 exomes AF: 0.572 AC: 143130 AN: 250396 AF XY: 0.568

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 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

African (AFR) AF: 0.857 AC: 28600 AN: 33370

American (AMR) AF: 0.554 AC: 24742 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 13810 AN: 26094

East Asian (EAS) AF: 0.977 AC: 38723 AN: 39646

South Asian (SAS) AF: 0.644 AC: 55490 AN: 86110

European-Finnish (FIN) AF: 0.456 AC: 24213 AN: 53106

Middle Eastern (MID) AF: 0.579 AC: 3331 AN: 5752

European-Non Finnish (NFE) AF: 0.476 AC: 526220 AN: 1106440

Other (OTH) AF: 0.553 AC: 33317 AN: 60194

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

African (AFR) AF: 0.844 AC: 35045 AN: 41522

American (AMR) AF: 0.557 AC: 8517 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1818 AN: 3462

East Asian (EAS) AF: 0.980 AC: 5073 AN: 5174

South Asian (SAS) AF: 0.667 AC: 3220 AN: 4824

European-Finnish (FIN) AF: 0.455 AC: 4805 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32319 AN: 67932

Other (OTH) AF: 0.600 AC: 1265 AN: 2110

Alfa AF: 0.477 Hom.: 8557

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
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1480544; hg19: chr4-170987636;