Genetic Variant ALG5:c.-34+352delT (chr13-37000344-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.208

Publications

0 publications found

Variant links:

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]

ALG5 links:

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

EXOSC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

Cov.:

AF XY:

0.397

AC XY:

384

AN XY:

968

show subpopulations

African (AFR)

AF:

0.464

AC:

AN:

American (AMR)

AF:

0.422

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

AN:

East Asian (EAS)

AF:

0.533

AC:

AN:

South Asian (SAS)

AF:

0.395

AC:

255

AN:

646

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.371

AC:

234

AN:

630

Other (OTH)

AF:

0.444

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.823

AC:

81392

AN:

98938

Hom.:

32686

Cov.:

AF XY:

0.825

AC XY:

38727

AN XY:

46934

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

481

962

1442

1923

2404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.531

Hom.:

767

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over