Variant 1-18885513-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003748.4(ALDH4A1):c.413C>G(p.Pro138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000287 in 1,395,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P138L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ALDH4A1
NM_003748.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.21

Variant links:

Genes affected

ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

ALDH4A1 links:

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ACMG classification

Classification made for transcript

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=0.26330987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALDH4A1	NM_003748.4 linkuse as main transcript	c.413C>G	p.Pro138Arg	missense_variant	5/15	ENST00000375341.8
ALDH4A1	NM_170726.3 linkuse as main transcript	c.413C>G	p.Pro138Arg	missense_variant	5/16
ALDH4A1	NM_001319218.2 linkuse as main transcript	c.413C>G	p.Pro138Arg	missense_variant	5/14
ALDH4A1	NM_001161504.2 linkuse as main transcript	c.233C>G	p.Pro78Arg	missense_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH4A1	ENST00000375341.8 linkuse as main transcript	c.413C>G	p.Pro138Arg	missense_variant	5/15	1	NM_003748.4	P1	P30038-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000894

AC:

AN:

223664

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1395438

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692416

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000373

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.070

T;.;T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.26

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.013

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.37

N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.073

T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;.

Polyphen

0.39

B;.;B;.;.

Vest4

0.59

MutPred

0.51

Gain of MoRF binding (P = 0.0031);Gain of MoRF binding (P = 0.0031);Gain of MoRF binding (P = 0.0031);.;.;

MVP

0.40

MPC

0.13

ClinPred

0.17

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over