rs368291171

Variant names:

• chr13-36995547-C-G
• rs368291171
• NM_013338.5:c.116G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-36995547-C-G
• chr13-36995547-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013338.5(ALG5):​c.116G>C​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG5 NM_013338.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 5 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG5	NM_013338.5	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 10	ENST00000239891.4	NP_037470.1
ALG5	NM_001142364.1	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 9		NP_001135836.1
ALG5	XR_007063678.1	n.156G>C		non_coding_transcript_exon_variant	Exon 2 of 9
ALG5	XM_047430283.1	c.-27G>C		5_prime_UTR_variant	Exon 1 of 8		XP_047286239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG5	ENST00000239891.4	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 10	1	NM_013338.5	ENSP00000239891.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	0.93
DANN	Benign	0.73
DEOGEN2	Uncertain	0.57	.;D
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	2.0	M;M
PhyloP100		-1.4
PrimateAI	Benign	0.17	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.97	D;D
Vest4		0.43
MutPred		0.48		Gain of catalytic residue at L37 (P = 0.0175);Gain of catalytic residue at L37 (P = 0.0175);
MVP		0.55
MPC		0.52
ClinPred		0.83	D
GERP RS		-12
Varity_R		0.34
gMVP		0.69
Mutation Taster		=70/30	polymorphism

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: rs368291171; hg19: chr13-37569684;