dbSNP rs372982045: ALG13:p.Val1133Val (chrX-111759984-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099922.3(ALG13):c.3399A>G(p.Val1133Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,208,770 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V1133V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.000036 ( 0 hom. 12 hem. )

Consequence

ALG13
NM_001099922.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0120

Publications

1 publications found

Variant links:

Genes affected

ALG13 (HGNC:30881): (ALG13 UDP-N-acetylglucosaminyltransferase subunit) The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ALG13 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 36
Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ALG13 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001099922.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-111759984-A-G is Benign according to our data. Variant chrX-111759984-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 512702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.012 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000448 (50/111517) while in subpopulation AFR AF = 0.00153 (47/30627). AF 95% confidence interval is 0.00118. There are 0 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 16 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG13	NM_001099922.3	MANE Select	c.3399A>G	p.Val1133Val	synonymous	Exon 27 of 27	NP_001093392.1	Q9NP73-1
ALG13	NM_001257231.2		c.3165A>G	p.Val1055Val	synonymous	Exon 27 of 27	NP_001244160.1	Q9NP73-3
ALG13	NM_001324292.2		c.3162A>G	p.Val1054Val	synonymous	Exon 26 of 26	NP_001311221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG13	ENST00000394780.8	TSL:2 MANE Select	c.3399A>G	p.Val1133Val	synonymous	Exon 27 of 27	ENSP00000378260.3	Q9NP73-1
ALG13	ENST00000927365.1		c.3375A>G	p.Val1125Val	synonymous	Exon 27 of 27	ENSP00000597424.1
ALG13	ENST00000927366.1		c.3225A>G	p.Val1075Val	synonymous	Exon 25 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes

AF:

0.000448

AC:

AN:

111517

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000124

AC:

AN:

177714

AF XY:

0.000107

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000355

AC:

AN:

1097253

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362805

show subpopulations

African (AFR)

AF:

0.000985

AC:

AN:

26388

American (AMR)

AF:

0.000199

AC:

AN:

35098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19355

East Asian (EAS)

AF:

0.00

AC:

AN:

30173

South Asian (SAS)

AF:

0.00

AC:

AN:

53960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841608

Other (OTH)

AF:

0.000109

AC:

AN:

46055

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000448

AC:

AN:

111517

Hom.:

Cov.:

AF XY:

0.000475

AC XY:

AN XY:

33719

show subpopulations

African (AFR)

AF:

0.00153

AC:

AN:

30627

American (AMR)

AF:

0.000287

AC:

AN:

10459

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3560

South Asian (SAS)

AF:

0.00

AC:

AN:

2646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5987

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53164

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000569

Hom.:

Bravo

AF:

0.000559

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy, 36 (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.0

(source)

DANN

Benign

0.61

PhyloP100

0.012

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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