5-126541967-G-GA

Position:

• chr5-126541967-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.99 (72560 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ALDH7A1 NM_001182.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B: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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-126541967-G-GA is Benign according to our data. Variant chr5-126541967-G-GA is described in ClinVar as [Benign]. Clinvar id is 350521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH7A1	NM_001182.5	c.*2997dupT		3_prime_UTR_variant	18/18	ENST00000409134.8	NP_001173.2
ALDH7A1	NM_001201377.2	c.*2997dupT		3_prime_UTR_variant	18/18		NP_001188306.1
ALDH7A1	NM_001202404.2	c.*2997dupT		3_prime_UTR_variant	16/16		NP_001189333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134	c.*2997dupT		3_prime_UTR_variant	18/18	1	NM_001182.5	ENSP00000387123.3
ALDH7A1	ENST00000635851.1	c.1563-980dupT		intron_variant		5		ENSP00000490819.1
ALDH7A1	ENST00000637782.1	c.1565+4356dupT		intron_variant		5		ENSP00000490024.1

Frequencies

GnomAD3 genomes AF: 0.993 AC: 146074 AN: 147092 Hom.: 72529 Cov.: 0

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.989

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: 0.993 AC: 146139 AN: 147160 Hom.: 72560 Cov.: 0 AF XY: 0.993 AC XY: 70955 AN XY: 71468

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.992

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.989

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pyridoxine-dependent epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;