Genetic Variant AADAT:c.963-7T>A (chr4-170066485-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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

Publications

21 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016228.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AADAT	NM_016228.4	MANE Select	c.963-7T>A	splice_region intron	N/A	NP_057312.1
AADAT	NM_001286682.2		c.975-7T>A	splice_region intron	N/A	NP_001273611.1
AADAT	NM_001286683.1		c.963-7T>A	splice_region intron	N/A	NP_001273612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AADAT	ENST00000337664.9	TSL:1 MANE Select	c.963-7T>A	splice_region intron	N/A	ENSP00000336808.4
AADAT	ENST00000509167.5	TSL:1	c.975-7T>A	splice_region intron	N/A	ENSP00000423190.1
AADAT	ENST00000515480.5	TSL:1	c.963-7T>A	splice_region intron	N/A	ENSP00000423341.1

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

GnomAD2 exomes

AF:

0.000395

AC:

AN:

250396

AF XY:

0.000532

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 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

African (AFR)

AF:

0.0000899

AC:

AN:

33388

American (AMR)

AF:

0.0000671

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.000186

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.0000753

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000507

AC:

562

AN:

1108910

Other (OTH)

AF:

0.000315

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000401

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41538

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000765

AC:

AN:

67952

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000100

Hom.:

8557

EpiCase

AF:

0.00120

EpiControl

AF:

0.000949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

(source)

DANN

Benign

0.61

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over