5-126541967-G-GA

Variant names:

• chr5-126541967-G-GA
• rs5871217
• NM_001182.5:c.*2997dupT

Variant summary

Our verdict is Benign. The variant received -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
• 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, Illumina, ClinGen
• pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*2997dupT		3_prime_UTR	Exon 18 of 18	NP_001173.2	P49419-1
	ALDH7A1	NM_001201377.2		c.*2997dupT		3_prime_UTR	Exon 18 of 18	NP_001188306.1	P49419-2
	ALDH7A1	NM_001202404.2		c.*2997dupT		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.*2997dupT		3_prime_UTR	Exon 18 of 18	ENSP00000387123.3	P49419-1
	ALDH7A1	ENST00000635851.1	TSL:5	c.1563-980dupT		intron	N/A	ENSP00000490819.1	A0A1B0GW82
	ALDH7A1	ENST00000637782.1	TSL:5	c.1565+4356dupT		intron	N/A	ENSP00000490024.1	A0A1B0GUA1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.993 AC: 146139 AN: 147160 Hom.: 72560 Cov.: 0 AF XY: 0.993 AC XY: 70955 AN XY: 71468

African (AFR) AF: 0.990 AC: 39917 AN: 40306

American (AMR) AF: 0.992 AC: 14683 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3419 AN: 3426

East Asian (EAS) AF: 0.995 AC: 5027 AN: 5052

South Asian (SAS) AF: 0.996 AC: 4672 AN: 4690

European-Finnish (FIN) AF: 0.983 AC: 8773 AN: 8928

Middle Eastern (MID) AF: 0.979 AC: 284 AN: 290

European-Non Finnish (NFE) AF: 0.996 AC: 66434 AN: 66720

Other (OTH) AF: 0.989 AC: 2027 AN: 2050

Alfa AF: 0.996 Hom.: 2139

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Pyridoxine-dependent epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5871217; hg19: chr5-125877659;