Variant 5-126540937-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBA1

The ENST00000635851.1(ALDH7A1):c.1614_1615insT(p.Thr540HisfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 23055 hom., cov: 0)

Exomes 𝑓: 0.59 ( 22 hom. )

Consequence

ALDH7A1
ENST00000635851.1 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.142

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0122 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 5-126540937-G-GA is Benign according to our data. Variant chr5-126540937-G-GA is described in ClinVar as [Benign]. Clinvar id is 3255247.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000635851.1 linkuse as main transcript	c.1614_1615insT	p.Thr540HisfsTer13	frameshift_variant	18/18	5		ENSP00000490819
ALDH7A1	ENST00000637782.1 linkuse as main transcript	c.1565+5386_1565+5387insT		intron_variant		5		ENSP00000490024

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

82021

AN:

147774

Hom.:

23032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.592

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.564

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.333

GnomAD4 genome

AF:

0.555

AC:

82081

AN:

147886

Hom.:

23055

Cov.:

AF XY:

0.555

AC XY:

39870

AN XY:

71870

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.551

Alfa

AF:

0.571

Hom.:

2710

Bravo

AF:

0.530

Asia WGS

AF:

0.517

AC:

1798

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 64. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over