chr13-37000544-C-T

Position:

• chr13-37000544-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+153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 561,718 control chromosomes in the GnomAD database, including 229,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63370 hom., cov: 31)
  • Exomes 𝑓: 0.90 (166297 hom.)
• Consequence: ALG5 ENST00000681893.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01

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=-0.8).
• BP6: Variant 13-37000544-C-T is Benign according to our data. Variant chr13-37000544-C-T is described in ClinVar as [Benign]. Clinvar id is 1243101.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+153G>A		intron_variant				ENSP00000506235
ALG5	ENST00000680949.1	c.-34+153G>A		intron_variant, NMD_transcript_variant				ENSP00000506156
EXOSC8	ENST00000489088.5	n.379+1350C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138612 AN: 152084 Hom.: 63313 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.920

GnomAD4 exome AF: 0.900 AC: 368751 AN: 409516 Hom.: 166297 Cov.: 3 AF XY: 0.903 AC XY: 195068 AN XY: 215950

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.905

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.952

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.909

GnomAD4 genome AF: 0.911 AC: 138727 AN: 152202 Hom.: 63370 Cov.: 31 AF XY: 0.912 AC XY: 67864 AN XY: 74400

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.920

Alfa AF: 0.893 Hom.: 7704

Bravo AF: 0.917

Asia WGS AF: 0.978 AC: 3402 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	-0.80
CADD	Benign	0.84
DANN	Benign	0.85

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: rs7334233; hg19: chr13-37574681;