NM_015423.3:c.383T>A

Variant names:

• chr11-106079666-T-A
• rs1023217274
• NM_015423.3:c.383T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015423.3(AASDHPPT):​c.383T>A​(p.Ile128Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I128T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AASDHPPT NM_015423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92

Genes affected

AASDHPPT (HGNC:14235): (aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase) The protein encoded by this gene is similar to Saccharomyces cerevisiae LYS5, which is required for the activation of the alpha-aminoadipate dehydrogenase in the biosynthetic pathway of lysine. Yeast alpha-aminoadipate dehydrogenase converts alpha-biosynthetic-aminoadipate semialdehyde to alpha-aminoadipate. It has been suggested that defects in the human gene result in pipecolic acidemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AASDHPPT	NM_015423.3	c.383T>A	p.Ile128Asn	missense_variant	Exon 2 of 6	ENST00000278618.9	NP_056238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AASDHPPT	ENST00000278618.9	c.383T>A	p.Ile128Asn	missense_variant	Exon 2 of 6	1	NM_015423.3	ENSP00000278618.4
AASDHPPT	ENST00000524411.5	c.188T>A	p.Ile63Asn	missense_variant	Exon 2 of 5	3		ENSP00000435099.1
AASDHPPT	ENST00000533423.5	c.188T>A	p.Ile63Asn	missense_variant	Exon 2 of 4	3		ENSP00000437175.1
AASDHPPT	ENST00000525660.1	n.383T>A		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000437144.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T;D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	2.9	.;.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.87
MutPred		0.86		.;.;Loss of stability (P = 0.0369);
MVP		0.81
MPC		1.4
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.94
gMVP		0.90

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: rs1023217274; hg19: chr11-105950393;