13-37000544-C-T

Variant names:

• chr13-37000544-C-T
• rs7334233
• ENST00000681893.1:c.-34+153G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 VariationId 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.

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
	EXOSC8	NM_181503.3	MANE Select	c.-262C>T		upstream_gene	N/A	NP_852480.1	Q96B26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG5	ENST00000681893.1		c.-34+153G>A		intron	N/A	ENSP00000506235.1	A0A7P0T901
	EXOSC8	ENST00000489088.5	TSL:3	n.379+1350C>T		intron	N/A
	ALG5	ENST00000680949.1		n.-34+153G>A		intron	N/A	ENSP00000506156.1	A0A7P0Z4I2

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

African (AFR) AF: 0.967 AC: 9893 AN: 10226

American (AMR) AF: 0.904 AC: 14361 AN: 15894

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 11330 AN: 12516

East Asian (EAS) AF: 1.00 AC: 26386 AN: 26394

South Asian (SAS) AF: 0.952 AC: 42302 AN: 44442

European-Finnish (FIN) AF: 0.886 AC: 24268 AN: 27378

Middle Eastern (MID) AF: 0.950 AC: 1739 AN: 1830

European-Non Finnish (NFE) AF: 0.878 AC: 216879 AN: 247080

Other (OTH) AF: 0.909 AC: 21593 AN: 23756

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

African (AFR) AF: 0.966 AC: 40123 AN: 41544

American (AMR) AF: 0.901 AC: 13782 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3133 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5164 AN: 5168

South Asian (SAS) AF: 0.955 AC: 4606 AN: 4822

European-Finnish (FIN) AF: 0.877 AC: 9278 AN: 10582

Middle Eastern (MID) AF: 0.962 AC: 281 AN: 292

European-Non Finnish (NFE) AF: 0.877 AC: 59618 AN: 68008

Other (OTH) AF: 0.920 AC: 1944 AN: 2112

Alfa AF: 0.893 Hom.: 7704

Bravo AF: 0.917

Asia WGS AF: 0.978 AC: 3402 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.84
DANN	Benign	0.85
PhyloP100		-1.0
PromoterAI		-0.12	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7334233; hg19: chr13-37574681;