chr13-36999270-G-C

Position:

chr13-36999270-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_013338.5(ALG5):c.31C>G(p.Leu11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,580,554 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

ALG5
NM_013338.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.55

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:

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

EXOSC8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016397238).

BP6

Variant 13-36999270-G-C is Benign according to our data. Variant chr13-36999270-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3040312.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000807 (123/152328) while in subpopulation NFE AF= 0.00116 (79/68030). AF 95% confidence interval is 0.000955. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 123 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG5	NM_013338.5 link	c.31C>G	p.Leu11Val	missense_variant	1/10	ENST00000239891.4	NP_037470.1	Q9Y673-1
ALG5	NM_001142364.1 link	c.31C>G	p.Leu11Val	missense_variant	1/9		NP_001135836.1	Q9Y673-2
ALG5	XR_007063678.1 link	n.71C>G		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG5	ENST00000239891.4 link	c.31C>G	p.Leu11Val	missense_variant	1/10	1	NM_013338.5	ENSP00000239891.3		Q9Y673-1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000998

AC:

207

AN:

207344

Hom.:

AF XY:

0.000996

AC XY:

115

AN XY:

115464

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00272

Gnomad NFE exome

AF:

0.00154

Gnomad OTH exome

AF:

0.000621

GnomAD4 exome

AF:

0.00110

AC:

1576

AN:

1428226

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

776

AN XY:

710402

show subpopulations

Gnomad4 AFR exome

AF:

0.000165

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152328

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000518

ExAC

AF:

0.000995

AC:

120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ALG5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 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

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.25

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.78

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.21

Sift

Benign

0.050

D;T

Sift4G

Uncertain

0.047

D;T

Polyphen

0.015

B;B

Vest4

0.42

MVP

0.70

MPC

0.42

ClinPred

0.044

GERP RS

3.6

Varity_R

0.10

gMVP

0.82

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