13-37000577-C-T

Position:

• chr13-37000577-C-T

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+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 597,566 control chromosomes in the GnomAD database, including 228,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52240 hom., cov: 33)
  • Exomes 𝑓: 0.89 (176655 hom.)
• Consequence: ALG5 ENST00000681893.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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=-0.82).
• BP6: Variant 13-37000577-C-T is Benign according to our data. Variant chr13-37000577-C-T is described in ClinVar as [Benign]. Clinvar id is 1290588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG5	ENST00000681893.1	c.-34+120G>A		intron_variant				ENSP00000506235
ALG5	ENST00000680949.1	c.-34+120G>A		intron_variant, NMD_transcript_variant				ENSP00000506156
EXOSC8	ENST00000489088.5	n.379+1383C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124931 AN: 152002 Hom.: 52216 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.889 AC: 396096 AN: 445446 Hom.: 176655 Cov.: 4 AF XY: 0.893 AC XY: 209869 AN XY: 234910

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.905

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.950

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.877

Gnomad4 OTH exome AF: 0.885

GnomAD4 genome AF: 0.822 AC: 124995 AN: 152120 Hom.: 52240 Cov.: 33 AF XY: 0.825 AC XY: 61359 AN XY: 74388

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.858

Alfa AF: 0.874 Hom.: 97626

Bravo AF: 0.814

Asia WGS AF: 0.956 AC: 3323 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	-0.82
CADD	Benign	0.44
DANN	Benign	0.79

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: rs9547715; hg19: chr13-37574714;