chr13-36996045-C-T

Variant names:

• chr13-36996045-C-T
• rs7989205
• NM_013338.5:c.67-449G>A

Variant summary

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

The NM_013338.5(ALG5):​c.67-449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,168 control chromosomes in the GnomAD database, including 52,409 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 0.82 (52409 hom., cov: 32)
• Consequence: ALG5 NM_013338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 4 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG5	NM_013338.5	c.67-449G>A		intron_variant	Intron 1 of 9	ENST00000239891.4	NP_037470.1
ALG5	NM_001142364.1	c.67-449G>A		intron_variant	Intron 1 of 8		NP_001135836.1
ALG5	XR_007063678.1	n.107-449G>A		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG5	ENST00000239891.4	c.67-449G>A		intron_variant	Intron 1 of 9	1	NM_013338.5	ENSP00000239891.3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125175 AN: 152050 Hom.: 52389 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.823 AC: 125234 AN: 152168 Hom.: 52409 Cov.: 32 AF XY: 0.826 AC XY: 61483 AN XY: 74396

African (AFR) AF: 0.658 AC: 27296 AN: 41478

American (AMR) AF: 0.870 AC: 13314 AN: 15296

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

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5170

South Asian (SAS) AF: 0.952 AC: 4595 AN: 4828

European-Finnish (FIN) AF: 0.877 AC: 9289 AN: 10590

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59557 AN: 68018

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

Alfa AF: 0.837 Hom.: 7838

Bravo AF: 0.816

Asia WGS AF: 0.954 AC: 3317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.088
DANN	Benign	0.61
PhyloP100		-1.3
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: rs7989205; hg19: chr13-37570182;