13-37000344-CAAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr13-37000344-C-CAA
• rs5802852
• ENST00000681893.1:c.-34+352_-34+353insTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000681893.1(ALG5):​c.-34+352_-34+353insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALG5 ENST00000681893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 0 publications found

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]

EXOSC8 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 1C

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681893.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG5	ENST00000681893.1		c.-34+352_-34+353insTT		intron	N/A	ENSP00000506235.1	A0A7P0T901
	EXOSC8	ENST00000489088.5	TSL:3	n.379+1150_379+1151insAA		intron	N/A
	ALG5	ENST00000680949.1		n.-34+352_-34+353insTT		intron	N/A	ENSP00000506156.1	A0A7P0Z4I2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 98898 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00472 AC: 7 AN: 1484 Hom.: 0 Cov.: 0 AF XY: 0.00413 AC XY: 4 AN XY: 968

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28

American (AMR) AF: 0.00 AC: 0 AN: 90

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 30

South Asian (SAS) AF: 0.00463 AC: 3 AN: 648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00637 AC: 4 AN: 628

Other (OTH) AF: 0.00 AC: 0 AN: 36

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000292915), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 98898 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 46884

African (AFR) AF: 0.00 AC: 0 AN: 27518

American (AMR) AF: 0.00 AC: 0 AN: 9870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2466

East Asian (EAS) AF: 0.00 AC: 0 AN: 3282

South Asian (SAS) AF: 0.00 AC: 0 AN: 2668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46342

Other (OTH) AF: 0.00 AC: 0 AN: 1278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5802852; hg19: chr13-37574481;