13-37000344-CA-C

Variant names:

• chr13-37000344-CA-C
• rs5802852
• ENST00000681893.1:c.-34+352delT

Variant summary

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

The ENST00000681893.1(ALG5):​c.-34+352delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (32686 hom., cov: 0)
  • Exomes 𝑓: 0.39 (9 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: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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-CA-C is Benign according to our data. Variant chr13-37000344-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1295035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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+352delT		intron	N/A	ENSP00000506235.1	A0A7P0T901
	EXOSC8	ENST00000489088.5	TSL:3	n.379+1151delA		intron	N/A
	ALG5	ENST00000680949.1		n.-34+352delT		intron	N/A	ENSP00000506156.1	A0A7P0Z4I2

Frequencies

GnomAD3 genomes AF: 0.823 AC: 81428 AN: 98960 Hom.: 32709 Cov.: 0

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.913

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.392 AC: 582 AN: 1484 Hom.: 9 Cov.: 0 AF XY: 0.397 AC XY: 384 AN XY: 968

African (AFR) AF: 0.464 AC: 13 AN: 28

American (AMR) AF: 0.422 AC: 38 AN: 90

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 5 AN: 12

East Asian (EAS) AF: 0.533 AC: 16 AN: 30

South Asian (SAS) AF: 0.395 AC: 255 AN: 646

European-Finnish (FIN) AF: 0.400 AC: 4 AN: 10

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.371 AC: 234 AN: 630

Other (OTH) AF: 0.444 AC: 16 AN: 36

GnomAD4 genome AF: 0.823 AC: 81392 AN: 98938 Hom.: 32686 Cov.: 0 AF XY: 0.825 AC XY: 38727 AN XY: 46934

African (AFR) AF: 0.825 AC: 22741 AN: 27558

American (AMR) AF: 0.831 AC: 8224 AN: 9892

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2079 AN: 2468

East Asian (EAS) AF: 0.954 AC: 3125 AN: 3274

South Asian (SAS) AF: 0.906 AC: 2394 AN: 2642

European-Finnish (FIN) AF: 0.804 AC: 3742 AN: 4652

Middle Eastern (MID) AF: 0.910 AC: 191 AN: 210

European-Non Finnish (NFE) AF: 0.805 AC: 37332 AN: 46352

Other (OTH) AF: 0.840 AC: 1075 AN: 1280

Alfa AF: 0.531 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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5802852; hg19: chr13-37574481;