NM_015423.3:c.308C>G

Variant names:

• chr11-106079591-C-G
• NM_015423.3:c.308C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015423.3(AASDHPPT):​c.308C>G​(p.Pro103Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. P103L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AASDHPPT NM_015423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.333009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AASDHPPT	NM_015423.3	c.308C>G	p.Pro103Arg	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.308C>G	p.Pro103Arg	missense_variant	Exon 2 of 6	1	NM_015423.3	ENSP00000278618.4
AASDHPPT	ENST00000524411.5	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 5	3		ENSP00000435099.1
AASDHPPT	ENST00000533423.5	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 4	3		ENSP00000437175.1
AASDHPPT	ENST00000525660.1	n.308C>G		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000437144.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.066	.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.9	.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.031	D;D;T
Polyphen		0.96	.;.;D
Vest4		0.30
MutPred		0.35		.;.;Gain of MoRF binding (P = 0.0654);
MVP		0.78
MPC		0.38
ClinPred		0.69	D
GERP RS		5.9
Varity_R		0.099
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-105950318;