rs12587903

chr14-74074615-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005589.4(ALDH6A1):c.111+340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,040 control chromosomes in the GnomAD database, including 2,609 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 0.17 (2609 hom., cov: 31)
• Consequence: ALDH6A1 NM_005589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

Genes affected

ALDH6A1 (HGNC:7179): (aldehyde dehydrogenase 6 family member A1) This gene encodes a member of the aldehyde dehydrogenase protein family. The encoded protein is a mitochondrial methylmalonate semialdehyde dehydrogenase that plays a role in the valine and pyrimidine catabolic pathways. This protein catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl- and propionyl-CoA. Methylmalonate semialdehyde dehydrogenase deficiency is characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

BBOF1 (HGNC:19855): (basal body orientation factor 1) Predicted to be involved in motile cilium assembly. Predicted to be located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH6A1	NM_005589.4	c.111+340A>G		intron_variant		ENST00000553458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH6A1	ENST00000553458.6	c.111+340A>G		intron_variant		1	NM_005589.4	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25309 AN: 151922 Hom.: 2600 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.167 AC: 25341 AN: 152040 Hom.: 2609 Cov.: 31 AF XY: 0.166 AC XY: 12354 AN XY: 74310

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.176

Alfa AF: 0.147 Hom.: 347

Bravo AF: 0.172

Asia WGS AF: 0.290 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	9.7
Dann	Benign	0.89

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: rs12587903; hg19: chr14-74541318;