5-126541967-G-GAA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001182.5(ALDH7A1):c.*2997_*2998insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ALDH7A1 NM_001182.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.632

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 Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00283 (416/146924) while in subpopulation AFR AF= 0.00467 (188/40288). AF 95% confidence interval is 0.00412. There are 0 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH7A1	NM_001182.5	c.*2997_*2998insTT		3_prime_UTR_variant	18/18	ENST00000409134.8
ALDH7A1	NM_001201377.2	c.*2997_*2998insTT		3_prime_UTR_variant	18/18
ALDH7A1	NM_001202404.2	c.*2997_*2998insTT		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH7A1	ENST00000409134.8	c.*2997_*2998insTT		3_prime_UTR_variant	18/18	1	NM_001182.5	P4
ALDH7A1	ENST00000635851.1	c.1564-980_1564-979insTT		intron_variant		5
ALDH7A1	ENST00000637782.1	c.1565+4356_1565+4357insTT		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 417 AN: 146860 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00441

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.000638

Gnomad FIN AF: 0.00328

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.00197

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00283 AC: 416 AN: 146924 Hom.: 0 Cov.: 0 AF XY: 0.00276 AC XY: 197 AN XY: 71322

Gnomad4 AFR AF: 0.00467

Gnomad4 AMR AF: 0.00440

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.000792

Gnomad4 SAS AF: 0.000427

Gnomad4 FIN AF: 0.00328

Gnomad4 NFE AF: 0.00177

Gnomad4 OTH AF: 0.00196

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pyridoxine-dependent epilepsy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs5871217; hg19: chr5-125877659;