6-24524476-C-T

Variant names:

• chr6-24524476-C-T
• rs807517
• NM_001080.3:c.1173+1551C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080.3(ALDH5A1):​c.1173+1551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,914 control chromosomes in the GnomAD database, including 3,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3941 hom., cov: 31)
• Consequence: ALDH5A1 NM_001080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 6 publications found

Genes affected

ALDH5A1 (HGNC:408): (aldehyde dehydrogenase 5 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ALDH5A1 Gene-Disease associations (from GenCC):

• succinic semialdehyde dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH5A1	NM_001080.3	MANE Select	c.1173+1551C>T		intron	N/A	NP_001071.1
	ALDH5A1	NM_170740.1		c.1212+1551C>T		intron	N/A	NP_733936.1
	ALDH5A1	NM_001368954.1		c.1029+1551C>T		intron	N/A	NP_001355883.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH5A1	ENST00000357578.8	TSL:1 MANE Select	c.1173+1551C>T		intron	N/A	ENSP00000350191.3
	ALDH5A1	ENST00000348925.2	TSL:1	c.1212+1551C>T		intron	N/A	ENSP00000314649.3
	ALDH5A1	ENST00000491546.5	TSL:5	c.1089+1551C>T		intron	N/A	ENSP00000417687.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33580 AN: 151794 Hom.: 3937 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33619 AN: 151914 Hom.: 3941 Cov.: 31 AF XY: 0.217 AC XY: 16111 AN XY: 74252

African (AFR) AF: 0.203 AC: 8424 AN: 41422

American (AMR) AF: 0.157 AC: 2403 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3472

East Asian (EAS) AF: 0.0997 AC: 514 AN: 5158

South Asian (SAS) AF: 0.141 AC: 679 AN: 4808

European-Finnish (FIN) AF: 0.278 AC: 2929 AN: 10544

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17363 AN: 67926

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.237 Hom.: 18499

Bravo AF: 0.213

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.43
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: rs807517; hg19: chr6-24524704;