Genetic Variant NM_015423.3:c.308C>G (chr11-106079591-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.72

Publications

0 publications found

Variant links:

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]

AASDHPPT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.333009).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015423.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AASDHPPT	NM_015423.3	MANE Select	c.308C>G	p.Pro103Arg	missense	Exon 2 of 6	NP_056238.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AASDHPPT	ENST00000278618.9	TSL:1 MANE Select	c.308C>G	p.Pro103Arg	missense	Exon 2 of 6	ENSP00000278618.4	Q9NRN7-1
AASDHPPT	ENST00000878108.1		c.317C>G	p.Pro106Arg	missense	Exon 2 of 6	ENSP00000548167.1
AASDHPPT	ENST00000926644.1		c.308C>G	p.Pro103Arg	missense	Exon 2 of 5	ENSP00000596703.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.70

M_CAP

Benign

0.0047

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

PhyloP100

5.7

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.23

Sift

Uncertain

0.026

Sift4G

Uncertain

0.031

Polyphen

0.96

Vest4

0.30

MutPred

0.35

Gain of MoRF binding (P = 0.0654)

MVP

0.78

MPC

0.38

ClinPred

0.69

GERP RS

5.9

Varity_R

0.099

gMVP

0.38

Mutation Taster

=53/47

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over