11-106077721-C-T

Variant names:

• chr11-106077721-C-T
• rs1414782237
• NM_015423.3:c.11C>T

Variant summary

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

The NM_015423.3(AASDHPPT):​c.11C>T​(p.Pro4Leu) 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. 14/20 in silico tools predict 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. P4R) 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: 0.109

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091575295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AASDHPPT	NM_015423.3	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 6	ENST00000278618.9	NP_056238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AASDHPPT	ENST00000278618.9	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 6	1	NM_015423.3	ENSP00000278618.4
AASDHPPT	ENST00000524411.5	c.-13+1433C>T		intron_variant	Intron 1 of 4	3		ENSP00000435099.1
AASDHPPT	ENST00000533423.5	c.-12-1746C>T		intron_variant	Intron 1 of 3	3		ENSP00000437175.1
AASDHPPT	ENST00000525660.1	n.11C>T		non_coding_transcript_exon_variant	Exon 1 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	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.038
Sift	Benign	0.19	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.41		Gain of sheet (P = 0.0085);
MVP		0.45
MPC		0.34
ClinPred		0.20	T
GERP RS		2.6
Varity_R		0.042
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1414782237; hg19: chr11-105948448;