chr13-37000577-C-T

Variant names:

• chr13-37000577-C-T
• rs9547715
• ENST00000681893.1:c.-34+120G>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+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 597,566 control chromosomes in the GnomAD database, including 228,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52240 hom., cov: 33)
  • Exomes 𝑓: 0.89 (176655 hom.)
• Consequence: ALG5 ENST00000681893.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• Publications: 11 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=-0.82).
• BP6: Variant 13-37000577-C-T is Benign according to our data. Variant chr13-37000577-C-T is described in ClinVar as Benign. ClinVar VariationId is 1290588.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.-229C>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+120G>A		intron	N/A	ENSP00000506235.1	A0A7P0T901
	EXOSC8	ENST00000489088.5	TSL:3	n.379+1383C>T		intron	N/A
	ALG5	ENST00000680949.1		n.-34+120G>A		intron	N/A	ENSP00000506156.1	A0A7P0Z4I2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124931 AN: 152002 Hom.: 52216 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.889 AC: 396096 AN: 445446 Hom.: 176655 Cov.: 4 AF XY: 0.893 AC XY: 209869 AN XY: 234910

African (AFR) AF: 0.663 AC: 7455 AN: 11250

American (AMR) AF: 0.883 AC: 15674 AN: 17754

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 12037 AN: 13304

East Asian (EAS) AF: 1.00 AC: 28539 AN: 28548

South Asian (SAS) AF: 0.950 AC: 43834 AN: 46118

European-Finnish (FIN) AF: 0.886 AC: 26303 AN: 29690

Middle Eastern (MID) AF: 0.934 AC: 1811 AN: 1938

European-Non Finnish (NFE) AF: 0.877 AC: 237818 AN: 271278

Other (OTH) AF: 0.885 AC: 22625 AN: 25566

GnomAD4 genome AF: 0.822 AC: 124995 AN: 152120 Hom.: 52240 Cov.: 33 AF XY: 0.825 AC XY: 61359 AN XY: 74388

African (AFR) AF: 0.654 AC: 27101 AN: 41456

American (AMR) AF: 0.870 AC: 13294 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3131 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5156 AN: 5160

South Asian (SAS) AF: 0.951 AC: 4593 AN: 4828

European-Finnish (FIN) AF: 0.876 AC: 9287 AN: 10596

Middle Eastern (MID) AF: 0.938 AC: 274 AN: 292

European-Non Finnish (NFE) AF: 0.876 AC: 59549 AN: 68006

Other (OTH) AF: 0.858 AC: 1812 AN: 2112

Alfa AF: 0.861 Hom.: 148405

Bravo AF: 0.814

Asia WGS AF: 0.956 AC: 3323 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	-0.82
CADD	Benign	0.44
DANN	Benign	0.79
PhyloP100		-1.2
PromoterAI		-0.013	Neutral
Mutation Taster		=300/0	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: rs9547715; hg19: chr13-37574714;