NM_013338.5:c.36C>G

Variant names:

• chr13-36999265-G-C
• rs146902400
• NM_013338.5:c.36C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_013338.5(ALG5):​c.36C>G​(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG5 NM_013338.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.293 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013338.5. 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
	ALG5	NM_013338.5	MANE Select	c.36C>G	p.Gly12Gly	synonymous	Exon 1 of 10	NP_037470.1	Q9Y673-1
	ALG5	NM_001142364.1		c.36C>G	p.Gly12Gly	synonymous	Exon 1 of 9	NP_001135836.1	Q9Y673-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG5	ENST00000239891.4	TSL:1 MANE Select	c.36C>G	p.Gly12Gly	synonymous	Exon 1 of 10	ENSP00000239891.3	Q9Y673-1
	ALG5	ENST00000857206.1		c.36C>G	p.Gly12Gly	synonymous	Exon 1 of 11	ENSP00000527265.1
	ALG5	ENST00000857208.1		c.36C>G	p.Gly12Gly	synonymous	Exon 1 of 10	ENSP00000527267.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.65
PhyloP100		0.29
PromoterAI		-0.073	Neutral

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: rs146902400; hg19: chr13-37573402;