13-37000571-G-A

Position:

• chr13-37000571-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.223

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]

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG5	ENST00000681893.1	c.-34+126C>T		intron_variant
ALG5	ENST00000680949.1	c.-34+126C>T		intron_variant, NMD_transcript_variant
EXOSC8	ENST00000489088.5	n.379+1377G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56440 AN: 151952 Hom.: 11463 Cov.: 33

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.: 4 AF XY: 0.426 AC XY: 97980 AN XY: 230188

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.: 33 AF XY: 0.370 AC XY: 27491 AN XY: 74316

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

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

Other links and lift over

dbSNP: rs9603126; hg19: chr13-37574708; COSMIC: COSV53508225; COSMIC: COSV53508225;