rs11188410

Positions:

• chr10-95636804-C-A
• chr10-95636804-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002860.4(ALDH18A1):​c.558+289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,276 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (297 hom., cov: 33)
• Consequence: ALDH18A1 NM_002860.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300

Genes affected

ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-95636804-C-A is Benign according to our data. Variant chr10-95636804-C-A is described in ClinVar as [Benign]. Clinvar id is 669715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH18A1	NM_002860.4	c.558+289G>T		intron_variant		ENST00000371224.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH18A1	ENST00000371224.7	c.558+289G>T		intron_variant		1	NM_002860.4	P3
ALDH18A1	ENST00000371221.3	c.558+289G>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9032 AN: 152158 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0593 AC: 9034 AN: 152276 Hom.: 297 Cov.: 33 AF XY: 0.0601 AC XY: 4476 AN XY: 74462

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.0449

Gnomad4 SAS AF: 0.0885

Gnomad4 FIN AF: 0.0764

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0553 Hom.: 232

Bravo AF: 0.0560

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.83
DANN	Benign	0.47

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: rs11188410; hg19: chr10-97396561;