rs34364382

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_144988.4(ALG14):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,130 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 101 hom. )

Consequence

ALG14
NM_144988.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.01

Publications

10 publications found

Variant links:

Genes affected

ALG14 (HGNC:28287): (ALG14 UDP-N-acetylglucosaminyltransferase subunit) This gene is a member of the glycosyltransferase 1 family. The encoded protein and ALG13 are thought to be subunits of UDP-GlcNAc transferase, which catalyzes the first two committed steps in endoplasmic reticulum N-linked glycosylation. Mutations in this gene have been linked to congenital myasthenic syndrome (CMSWTA). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ALG14 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 15
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
myopathy, epilepsy, and progressive cerebral atrophy
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myasthenic syndromes with glycosylation defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital disorder of glycosylation
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ALG14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038206875).

BP6

Variant 1-95072868-C-T is Benign according to our data. Variant chr1-95072868-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144988.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG14	NM_144988.4	MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 4	NP_659425.1	Q96F25
ALG14	NM_001305242.2		c.31G>A	p.Ala11Thr	missense	Exon 1 of 5	NP_001292171.1
ALG14	NR_131032.2		n.84G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG14	ENST00000370205.6	TSL:1 MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 4	ENSP00000359224.4	Q96F25
ALG14	ENST00000897799.1		c.31G>A	p.Ala11Thr	missense	Exon 1 of 3	ENSP00000567858.1
ALG14	ENST00000495856.1	TSL:3	n.7G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00718

AC:

1804

AN:

251340

AF XY:

0.00740

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00624

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00880

GnomAD4 exome

AF:

0.0110

AC:

16126

AN:

1461826

Hom.:

101

Cov.:

AF XY:

0.0108

AC XY:

7881

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

33478

American (AMR)

AF:

0.00577

AC:

258

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00195

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00482

AC:

416

AN:

86256

European-Finnish (FIN)

AF:

0.00704

AC:

376

AN:

53380

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0129

AC:

14379

AN:

1111998

Other (OTH)

AF:

0.00931

AC:

562

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

932

1864

2796

3728

4660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

566

1132

1698

2264

2830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00745

AC:

1134

AN:

152304

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41584

American (AMR)

AF:

0.0110

AC:

169

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00575

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

763

AN:

68030

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

126

188

251

314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00939

Hom.:

Bravo

AF:

0.00740

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0117

AC:

101

ExAC

AF:

0.00694

AC:

843

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.00954

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Congenital myasthenic syndrome 15 (2)

ALG14-related disorder (1)

Congenital myasthenic syndrome 15;C5436646:Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies;C5436652:Myopathy, epilepsy, and progressive cerebral atrophy (1)

Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (1)

Myopathy, epilepsy, and progressive cerebral atrophy (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.74

REVEL

Benign

0.017

Sift

Benign

0.071

Sift4G

Benign

0.10

Polyphen

0.016

Vest4

0.18

MVP

0.25

MPC

0.35

ClinPred

0.012

GERP RS

3.3

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.050

gMVP

0.66

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over