chr5-126540937-G-GA

Variant names:

• chr5-126540937-G-GA
• rs34011388
• ENST00000635851.1:c.1613dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_Moderate BP6_Moderate BA1

The ENST00000635851.1(ALDH7A1):​c.1613dupT​(p.Thr539fs) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.142

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]

ACMG classification

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 0.0135 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000635851.1	c.1613dupT	p.Thr539fs	frameshift_variant	Exon 18 of 18	5		ENSP00000490819.1
ALDH7A1	ENST00000637782.1	c.1565+5386dupT		intron_variant	Intron 17 of 17	5		ENSP00000490024.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 82021 AN: 147774 Hom.: 23032 Cov.: 0

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: 77 AN: 130 Hom.: 22 Cov.: 0 AF XY: 0.564 AC XY: 44 AN XY: 78

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.: 0 AF XY: 0.555 AC XY: 39870 AN XY: 71870

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

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34011388; hg19: chr5-125876629;