Variant chr13-37000571-G-A 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 ENST00000681893.1(ALG5):c.-34+126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 588,562 control chromosomes in the GnomAD database, including 52,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11463 hom., cov: 33)

Exomes 𝑓: 0.43 ( 41071 hom. )

Consequence

ALG5
ENST00000681893.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

ALG5 (HGNC:20266): (ALG5 dolichyl-phosphate beta-glucosyltransferase) This gene encodes a member of the glycosyltransferase 2 family. The encoded protein participates in glucosylation of the oligomannose core in N-linked glycosylation of proteins. The addition of glucose residues to the oligomannose core is necessary to ensure substrate recognition, and therefore, effectual transfer of the oligomannose core to the nascent glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ALG5 links:

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

EXOSC8 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=-0.78).

BP6

Variant 13-37000571-G-A is Benign according to our data. Variant chr13-37000571-G-A is described in ClinVar as [Benign]. Clinvar id is 1259426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
ALG5	ENST00000681893.1 linkuse as main transcript	c.-34+126C>T	intron_variant
ALG5	ENST00000680949.1 linkuse as main transcript	c.-34+126C>T	intron_variant, NMD_transcript_variant
EXOSC8	ENST00000489088.5 linkuse as main transcript	n.379+1377G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56440

AN:

151952

Hom.:

11463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.419

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.427

AC:

186579

AN:

436490

Hom.:

41071

Cov.:

AF XY:

0.426

AC XY:

97980

AN XY:

230188

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.448

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.371

AC:

56437

AN:

152072

Hom.:

11463

Cov.:

AF XY:

0.370

AC XY:

27491

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.412

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.438

Hom.:

7034

Bravo

AF:

0.363

Asia WGS

AF:

0.288

AC:

1002

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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