Genetic Variant AADAT:c.963-7T>A (chr4-170066485-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016228.4(AADAT):c.963-7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,610,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

AADAT
NM_016228.4 splice_region, intron

Scores

Splicing: ADA: 0.0001093

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.859

Variant links:

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]

AADAT links:

LOC107986326 (HGNC:):

LOC107986326 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AADAT	NM_016228.4 link	c.963-7T>A		splice_region_variant, intron_variant	Intron 9 of 12	ENST00000337664.9	NP_057312.1	Q8N5Z0-1Q4W5N8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AADAT	ENST00000337664.9 link	c.963-7T>A	splice_region_variant, intron_variant	Intron 9 of 12	1	NM_016228.4	ENSP00000336808.4	Q8N5Z0-1
AADAT	ENST00000509167.5 link	c.975-7T>A	splice_region_variant, intron_variant	Intron 10 of 13	1		ENSP00000423190.1	Q8N5Z0-2
AADAT	ENST00000515480.5 link	c.963-7T>A	splice_region_variant, intron_variant	Intron 10 of 13	1		ENSP00000423341.1	Q8N5Z0-1
AADAT	ENST00000353187.6 link	c.963-7T>A	splice_region_variant, intron_variant	Intron 10 of 13	2		ENSP00000226840.4	Q8N5Z0-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000395

AC:

AN:

250396

Hom.:

AF XY:

0.000532

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000725

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000420

AC:

613

AN:

1458082

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

331

AN XY:

725556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000753

Gnomad4 NFE exome

AF:

0.000507

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000401

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

4828

EpiCase

AF:

0.00120

EpiControl

AF:

0.000949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over