dbSNP rs772766102: ALG13:p.Glu795del (chrX-111730405-TGAA-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2383_2385delGAA(p.Glu795del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000907 in 1,208,532 control chromosomes in the GnomAD database, including 1 homozygotes. There are 330 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E795E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., 18 hem., cov: 23)

Exomes 𝑓: 0.00094 ( 1 hom. 312 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 4.48

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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ALG13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001099922.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-111730405-TGAA-T is Benign according to our data. Variant chrX-111730405-TGAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000604 (68/112490) while in subpopulation NFE AF = 0.000976 (52/53284). AF 95% confidence interval is 0.000764. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 18 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.2383_2385delGAA	p.Glu795del	conservative_inframe_deletion	Exon 20 of 27	NP_001093392.1	Q9NP73-1
ALG13	NM_001257231.2		c.2149_2151delGAA	p.Glu717del	conservative_inframe_deletion	Exon 20 of 27	NP_001244160.1	Q9NP73-3
ALG13	NM_001324292.2		c.2383_2385delGAA	p.Glu795del	conservative_inframe_deletion	Exon 20 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.2383_2385delGAA	p.Glu795del	conservative_inframe_deletion	Exon 20 of 27	ENSP00000378260.3	Q9NP73-1
ALG13	ENST00000927365.1		c.2359_2361delGAA	p.Glu787del	conservative_inframe_deletion	Exon 20 of 27	ENSP00000597424.1
ALG13	ENST00000927366.1		c.2209_2211delGAA	p.Glu737del	conservative_inframe_deletion	Exon 18 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

112490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

Gnomad ASJ

AF:

0.00377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000976

Gnomad OTH

AF:

0.00131

GnomAD2 exomes

AF:

0.000439

AC:

AN:

177526

AF XY:

0.000366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000735

Gnomad ASJ exome

AF:

0.00324

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.000613

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.000938

AC:

1028

AN:

1096042

Hom.:

AF XY:

0.000863

AC XY:

312

AN XY:

361688

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26369

American (AMR)

AF:

0.0000854

AC:

AN:

35139

Ashkenazi Jewish (ASJ)

AF:

0.00393

AC:

AN:

19358

East Asian (EAS)

AF:

0.00

AC:

AN:

30171

South Asian (SAS)

AF:

0.00

AC:

AN:

53944

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

40469

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4073

European-Non Finnish (NFE)

AF:

0.00107

AC:

903

AN:

840522

Other (OTH)

AF:

0.000783

AC:

AN:

45997

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.000604

AC:

AN:

112490

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

AN XY:

34654

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31008

American (AMR)

AF:

0.000283

AC:

AN:

10595

Ashkenazi Jewish (ASJ)

AF:

0.00377

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

2744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000976

AC:

AN:

53284

Other (OTH)

AF:

0.00131

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.00127

Hom.:

Bravo

AF:

0.000476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (7)

Developmental and epileptic encephalopathy, 36 (2)

ALG13-related disorder (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.5

Mutation Taster

=79/21

polymorphism

(source)

Splicing

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