Variant chr13-36995455-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_013338.5(ALG5):c.208G>A(p.Val70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,612,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

ALG5
NM_013338.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications B:1

Conservation

PhyloP100: 0.928

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016423345).

BP6

Variant 13-36995455-C-T is Benign according to our data. Variant chr13-36995455-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3054996.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1}.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALG5	NM_013338.5 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	2/10	ENST00000239891.4
ALG5	NM_001142364.1 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	2/9
ALG5	XM_047430283.1 linkuse as main transcript	c.66G>A	p.Ser22=	synonymous_variant	1/8
ALG5	XR_007063678.1 linkuse as main transcript	n.248G>A		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG5	ENST00000239891.4 linkuse as main transcript	c.208G>A	p.Val70Ile	missense_variant	2/10	1	NM_013338.5	P1	Q9Y673-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250038

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000760

AC:

111

AN:

1460514

Hom.:

Cov.:

AF XY:

0.0000785

AC XY:

AN XY:

726474

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000361

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

ALG5-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0083

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.0050

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.038

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.067

B;B

Vest4

0.14

MVP

0.21

MPC

0.29

ClinPred

0.013

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over