dbSNP rs549279821: ALDH7A1:p.Ala120Val (chr5-126583966-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001182.5(ALDH7A1):c.359C>T(p.Ala120Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ALDH7A1
NM_001182.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.30

Variant links:

Genes affected

ALDH7A1 (HGNC:877): (aldehyde dehydrogenase 7 family member A1) The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified. [provided by RefSeq, Jan 2011]

ALDH7A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH7A1	NM_001182.5 link	c.359C>T	p.Ala120Val	missense_variant	Exon 4 of 18	ENST00000409134.8	NP_001173.2	P49419-1
ALDH7A1	NM_001201377.2 link	c.275C>T	p.Ala92Val	missense_variant	Exon 4 of 18		NP_001188306.1	P49419-2
ALDH7A1	NM_001202404.2 link	c.359C>T	p.Ala120Val	missense_variant	Exon 4 of 16		NP_001189333.2	P49419-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8 link	c.359C>T	p.Ala120Val	missense_variant	Exon 4 of 18	1	NM_001182.5	ENSP00000387123.3		P49419-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251476

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;D;T;.;.;.;.;T;T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.57

MutationAssessor

Uncertain

2.3

.;M;.;.;.;.;M;.;.;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

.;D;.;.;.;.;D;.;.;.

REVEL

Pathogenic

0.70

Sift

Benign

0.13

.;T;.;.;.;.;T;.;.;.

Sift4G

Benign

0.23

.;T;.;.;.;.;T;.;T;.

Polyphen

1.0

.;D;.;.;.;.;.;.;.;.

Vest4

0.76, 0.74, 0.76

MutPred

0.52

Gain of MoRF binding (P = 0.1137);Gain of MoRF binding (P = 0.1137);Gain of MoRF binding (P = 0.1137);Gain of MoRF binding (P = 0.1137);Gain of MoRF binding (P = 0.1137);.;Gain of MoRF binding (P = 0.1137);.;Gain of MoRF binding (P = 0.1137);.;

MVP

0.97

MPC

0.62

ClinPred

0.91

GERP RS

4.3

Varity_R

0.42

gMVP

0.66

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

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