chr13-37000344-CAA-C

Variant names:

• chr13-37000344-CAA-C
• rs5802852
• ENST00000681893.1:c.-34+351_-34+352delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000681893.1(ALG5):​c.-34+351_-34+352delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 100,342 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (21 hom., cov: 0)
  • Exomes 𝑓: 0.16 (0 hom.)
• Consequence: ALG5 ENST00000681893.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-37000344-CAA-C is Benign according to our data. Variant chr13-37000344-CAA-C is described in ClinVar as Benign. ClinVar VariationId is 1275077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

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+351_-34+352delTT		intron	N/A	ENSP00000506235.1	A0A7P0T901
	EXOSC8	ENST00000489088.5	TSL:3	n.379+1151_379+1152delAA		intron	N/A
	ALG5	ENST00000680949.1		n.-34+351_-34+352delTT		intron	N/A	ENSP00000506156.1	A0A7P0Z4I2

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 1652 AN: 98892 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00750

Gnomad ASJ AF: 0.000811

Gnomad EAS AF: 0.00305

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00798

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.00627

GnomAD4 exome AF: 0.160 AC: 235 AN: 1472 Hom.: 0 AF XY: 0.155 AC XY: 149 AN XY: 960

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

African (AFR) AF: 0.269 AC: 7 AN: 26

American (AMR) AF: 0.211 AC: 19 AN: 90

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 2 AN: 12

East Asian (EAS) AF: 0.167 AC: 5 AN: 30

South Asian (SAS) AF: 0.159 AC: 102 AN: 640

European-Finnish (FIN) AF: 0.100 AC: 1 AN: 10

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

European-Non Finnish (NFE) AF: 0.152 AC: 95 AN: 626

Other (OTH) AF: 0.111 AC: 4 AN: 36

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0167 AC: 1655 AN: 98870 Hom.: 21 Cov.: 0 AF XY: 0.0165 AC XY: 776 AN XY: 46892

African (AFR) AF: 0.0532 AC: 1467 AN: 27582

American (AMR) AF: 0.00750 AC: 74 AN: 9872

Ashkenazi Jewish (ASJ) AF: 0.000811 AC: 2 AN: 2466

East Asian (EAS) AF: 0.00306 AC: 10 AN: 3268

South Asian (SAS) AF: 0.00114 AC: 3 AN: 2642

European-Finnish (FIN) AF: 0.00798 AC: 37 AN: 4634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00117 AC: 54 AN: 46310

Other (OTH) AF: 0.00626 AC: 8 AN: 1278

Alfa AF: 0.00 Hom.: 767

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;