5-126542144-T-TAA

Variant names:

• chr5-126542144-T-TAA
• rs886059832
• NM_001182.5:c.*2820_*2821insTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001182.5(ALDH7A1):​c.*2820_*2821insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: ALDH7A1 NM_001182.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001182.5. 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
	ALDH7A1	NM_001182.5	MANE Select	c.*2820_*2821insTT		3_prime_UTR	Exon 18 of 18	NP_001173.2	P49419-1
	ALDH7A1	NM_001201377.2		c.*2820_*2821insTT		3_prime_UTR	Exon 18 of 18	NP_001188306.1	P49419-2
	ALDH7A1	NM_001202404.2		c.*2820_*2821insTT		3_prime_UTR	Exon 16 of 16	NP_001189333.2	P49419-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	ENST00000409134.8	TSL:1 MANE Select	c.*2820_*2821insTT		3_prime_UTR	Exon 18 of 18	ENSP00000387123.3	P49419-1
	ALDH7A1	ENST00000635851.1	TSL:5	c.1563-1157_1563-1156insTT		intron	N/A	ENSP00000490819.1	A0A1B0GW82
	ALDH7A1	ENST00000637782.1	TSL:5	c.1565+4179_1565+4180insTT		intron	N/A	ENSP00000490024.1	A0A1B0GUA1

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 1 AN: 68812 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000145 AC: 1 AN: 68812 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 31906

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000599 AC: 1 AN: 16706

American (AMR) AF: 0.00 AC: 0 AN: 5038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1662

East Asian (EAS) AF: 0.00 AC: 0 AN: 2034

South Asian (SAS) AF: 0.00 AC: 0 AN: 2440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 82

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36356

Other (OTH) AF: 0.00 AC: 0 AN: 848

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs886059832; hg19: chr5-125877836;