NM_013338.5:c.926G>T

Variant names:

• chr13-36949991-C-A
• rs370016246
• NM_013338.5:c.926G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013338.5(ALG5):​c.926G>T​(p.Arg309Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R309Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG5 NM_013338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61
• 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]

ALG5 Gene-Disease associations (from GenCC):

• polycystic kidney disease 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.926G>T	p.Arg309Leu	missense	Exon 10 of 10	NP_037470.1	Q9Y673-1
	ALG5	NM_001142364.1		c.836G>T	p.Arg279Leu	missense	Exon 9 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.926G>T	p.Arg309Leu	missense	Exon 10 of 10	ENSP00000239891.3	Q9Y673-1
	ALG5	ENST00000857206.1		c.1019G>T	p.Arg340Leu	missense	Exon 11 of 11	ENSP00000527265.1
	ALG5	ENST00000857208.1		c.905G>T	p.Arg302Leu	missense	Exon 10 of 10	ENSP00000527267.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.13	T
Polyphen		0.73	P
Vest4		0.76
MutPred		0.69		Gain of catalytic residue at A314 (P = 0.0014)
MVP		0.78
MPC		0.41
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.98
Mutation Taster		=20/80	disease causing

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: rs370016246; hg19: chr13-37524128;