13-36975791-T-G

Variant names:

• chr13-36975791-T-G
• rs8001724
• NM_013338.5:c.562-3755A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013338.5(ALG5):​c.562-3755A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 151,992 control chromosomes in the GnomAD database, including 1,381 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.073 (1381 hom., cov: 32)
• Consequence: ALG5 NM_013338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

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.562-3755A>C		intron	N/A	NP_037470.1	Q9Y673-1
	ALG5	NM_001142364.1		c.472-3755A>C		intron	N/A	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.562-3755A>C		intron	N/A	ENSP00000239891.3	Q9Y673-1
	ALG5	ENST00000857206.1		c.624A>C	p.Pro208Pro	synonymous	Exon 7 of 11	ENSP00000527265.1
	ALG5	ENST00000857208.1		c.510A>C	p.Pro170Pro	synonymous	Exon 6 of 10	ENSP00000527267.1

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11079 AN: 151874 Hom.: 1363 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0489

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0732 AC: 11126 AN: 151992 Hom.: 1381 Cov.: 32 AF XY: 0.0708 AC XY: 5264 AN XY: 74340

African (AFR) AF: 0.254 AC: 10540 AN: 41418

American (AMR) AF: 0.0271 AC: 414 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4814

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10588

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67966

Other (OTH) AF: 0.0484 AC: 102 AN: 2106

Alfa AF: 0.0236 Hom.: 38

Bravo AF: 0.0842

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		-0.34
Mutation Taster		=100/0	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: rs8001724; hg19: chr13-37549928;