Variant 12-34025895-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032834.4(ALG10):c.402A>C(p.Thr134Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,004 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 33 hom. )

Consequence

ALG10
NM_032834.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

ALG10 (HGNC:23162): (ALG10 alpha-1,2-glucosyltransferase) This gene encodes a membrane-associated protein that adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. That is, it transfers the terminal glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc2Man9GlcNAc(2)-PP-Dol. The rat protein homolog was shown to specifically modulate the gating function of the rat neuronal ether-a-go-go (EAG) potassium ion channel. [provided by RefSeq, Jan 2010]

ALG10 links:

ENSG00000245482 (HGNC:):

ENSG00000245482 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 12-34025895-A-C is Benign according to our data. Variant chr12-34025895-A-C is described in ClinVar as [Benign]. Clinvar id is 785400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1748/152252) while in subpopulation AFR AF= 0.0388 (1613/41548). AF 95% confidence interval is 0.0372. There are 38 homozygotes in gnomad4. There are 809 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG10	NM_032834.4 link	c.402A>C	p.Thr134Thr	synonymous_variant	3/3	ENST00000266483.7	NP_116223.3	Q5BKT4
ALG10	XM_024449230.2 link	c.222A>C	p.Thr74Thr	synonymous_variant	3/3		XP_024304998.1
ALG10	XM_024449231.2 link	c.222A>C	p.Thr74Thr	synonymous_variant	3/3		XP_024304999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG10	ENST00000266483.7 link	c.402A>C	p.Thr134Thr	synonymous_variant	3/3	1	NM_032834.4	ENSP00000266483.2		Q5BKT4

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1743

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00335

AC:

842

AN:

251106

Hom.:

AF XY:

0.00255

AC XY:

346

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0389

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00844

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00144

AC:

2106

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

971

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0415

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.00918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.0115

AC:

1748

AN:

152252

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

809

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 03, 2018	- -

ALG10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.8

DANN

Benign

0.85

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