4-170086353-C-T

Variant names:

• chr4-170086353-C-T
• rs716822
• NM_016228.4:c.369+763G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016228.4(AADAT):​c.369+763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,928 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (907 hom., cov: 32)
• Consequence: AADAT NM_016228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 1 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]

ENSG00000296173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AADAT	NM_016228.4	c.369+763G>A		intron_variant	Intron 3 of 12	ENST00000337664.9	NP_057312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AADAT	ENST00000337664.9	c.369+763G>A		intron_variant	Intron 3 of 12	1	NM_016228.4	ENSP00000336808.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15548 AN: 151820 Hom.: 906 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15566 AN: 151928 Hom.: 907 Cov.: 32 AF XY: 0.0966 AC XY: 7177 AN XY: 74260

African (AFR) AF: 0.144 AC: 5954 AN: 41410

American (AMR) AF: 0.0831 AC: 1270 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5150

South Asian (SAS) AF: 0.0798 AC: 384 AN: 4810

European-Finnish (FIN) AF: 0.0375 AC: 396 AN: 10564

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.100 AC: 6812 AN: 67948

Other (OTH) AF: 0.106 AC: 223 AN: 2096

Alfa AF: 0.0466 Hom.: 52

Bravo AF: 0.107

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		0.054
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs716822; hg19: chr4-171007504;