4-170087177-G-T

Position:

• chr4-170087177-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016228.4(AADAT):​c.308C>A​(p.Pro103Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AADAT NM_016228.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13711324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADAT	NM_016228.4	c.308C>A	p.Pro103Gln	missense_variant	3/13	ENST00000337664.9	NP_057312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADAT	ENST00000337664.9	c.308C>A	p.Pro103Gln	missense_variant	3/13	1	NM_016228.4	ENSP00000336808.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.46	T;.;T;T;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.87	.;D;.;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;L;L;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.36	N;N;N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.060	T;D;T;T;T;T;T
Sift4G	Benign	0.085	T;T;T;T;.;.;T
Polyphen		0.048	B;B;B;B;.;.;.
Vest4		0.29
MutPred		0.41		Loss of catalytic residue at P103 (P = 0.0168);.;Loss of catalytic residue at P103 (P = 0.0168);Loss of catalytic residue at P103 (P = 0.0168);.;Loss of catalytic residue at P103 (P = 0.0168);Loss of catalytic residue at P103 (P = 0.0168);
MVP		0.50
MPC		1.2
ClinPred		0.39	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs17852900; hg19: chr4-171008328;