rs34011388

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• pyridoxine-dependent epilepsy

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, Illumina
• pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635851.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	ENST00000635851.1	TSL:5	c.1613dupT	p.Thr539fs	frameshift	Exon 18 of 18	ENSP00000490819.1	A0A1B0GW82
	ALDH7A1	ENST00000637782.1	TSL:5	c.1565+5386dupT		intron	N/A	ENSP00000490024.1	A0A1B0GUA1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.629 AC: 73 AN: 116

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 4 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.555 AC: 82081 AN: 147886 Hom.: 23055 Cov.: 0 AF XY: 0.555 AC XY: 39870 AN XY: 71870

African (AFR) AF: 0.485 AC: 19292 AN: 39818

American (AMR) AF: 0.480 AC: 7029 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2220 AN: 4950

South Asian (SAS) AF: 0.624 AC: 2880 AN: 4616

European-Finnish (FIN) AF: 0.626 AC: 6067 AN: 9684

Middle Eastern (MID) AF: 0.552 AC: 160 AN: 290

European-Non Finnish (NFE) AF: 0.609 AC: 41079 AN: 67478

Other (OTH) AF: 0.551 AC: 1132 AN: 2056

Alfa AF: 0.571 Hom.: 2710

Bravo AF: 0.530

Asia WGS AF: 0.517 AC: 1798 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs34011388; hg19: chr5-125876629;