Genetic Variant ALG13:p.Pro943_Pro945del (chrX-111744768-ACCTCCTCCT-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2827_2835delCCTCCTCCT(p.Pro943_Pro945del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 594,303 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 0 hem., cov: 9)

Exomes 𝑓: 0.00020 ( 0 hom. 28 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.290

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-111744768-ACCTCCTCCT-A is Benign according to our data. Variant chrX-111744768-ACCTCCTCCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 648499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000215 (8/37156) while in subpopulation SAS AF= 0.00186 (1/537). AF 95% confidence interval is 0.000198. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 9. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 28 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2827_2835delCCTCCTCCT	p.Pro943_Pro945del	conservative_inframe_deletion	Exon 24 of 27	ENST00000394780.8	NP_001093392.1	Q9NP73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 link	c.2827_2835delCCTCCTCCT	p.Pro943_Pro945del	conservative_inframe_deletion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

37160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7144

show subpopulations

Gnomad AFR

AF:

0.000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00185

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000502

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000201

AC:

112

AN:

557147

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

158423

show subpopulations

Gnomad4 AFR exome

AF:

0.000207

Gnomad4 AMR exome

AF:

0.000787

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.000721

Gnomad4 FIN exome

AF:

0.000108

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.000164

GnomAD4 genome

AF:

0.000215

AC:

AN:

37156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7144

show subpopulations

Gnomad4 AFR

AF:

0.000503

Gnomad4 AMR

AF:

0.000397

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000502

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 11, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCT

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