Variant 10-95606607-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002860.4(ALDH18A1):c.*155G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,579,346 control chromosomes in the GnomAD database, including 203,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15315 hom., cov: 32)

Exomes 𝑓: 0.50 ( 188414 hom. )

Consequence

ALDH18A1
NM_002860.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0270

Variant links:

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]

ALDH18A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-95606607-C-T is Benign according to our data. Variant chr10-95606607-C-T is described in ClinVar as [Benign]. Clinvar id is 301753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH18A1	NM_002860.4 linkuse as main transcript	c.*155G>A		3_prime_UTR_variant	18/18	ENST00000371224.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH18A1	ENST00000371224.7 linkuse as main transcript	c.*155G>A		3_prime_UTR_variant	18/18	1	NM_002860.4	P3	P54886-1
ALDH18A1	ENST00000371221.3 linkuse as main transcript	c.*155G>A		3_prime_UTR_variant	18/18	1		A1	P54886-2

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63902

AN:

151962

Hom.:

15331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.503

AC:

718183

AN:

1427266

Hom.:

188414

Cov.:

AF XY:

0.498

AC XY:

352518

AN XY:

707796

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.0876

Gnomad4 SAS exome

AF:

0.323

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.420

AC:

63876

AN:

152080

Hom.:

15315

Cov.:

AF XY:

0.418

AC XY:

31045

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.0847

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.485

Hom.:

7046

Bravo

AF:

0.416

Asia WGS

AF:

0.179

AC:

627

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

ALDH18A1-related de Barsy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over