X-111744771-T-C

Variant names:

• chrX-111744771-T-C
• rs13440710
• NM_001099922.3:c.2799T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001099922.3(ALG13):​c.2799T>C​(p.Pro933Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. P933P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., 0 hem., cov: 9)
  • Exomes 𝑓: 0.000013 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.799
• Publications: 4 publications found

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, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-111744771-T-C is Benign according to our data. Variant chrX-111744771-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3015163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.799 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.2799T>C	p.Pro933Pro	synonymous_variant	Exon 24 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.2799T>C	p.Pro933Pro	synonymous_variant	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.0000226 AC: 1 AN: 44342 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 0.0000128 AC: 3 AN: 234376 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 63870

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5472

American (AMR) AF: 0.00 AC: 0 AN: 7218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3127

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 8773

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6877

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 596

European-Non Finnish (NFE) AF: 0.0000160 AC: 3 AN: 188064

Other (OTH) AF: 0.00 AC: 0 AN: 9259

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000225 AC: 1 AN: 44352 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 8756

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000101 AC: 1 AN: 9908

American (AMR) AF: 0.00 AC: 0 AN: 3215

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1228

East Asian (EAS) AF: 0.00 AC: 0 AN: 1409

South Asian (SAS) AF: 0.00 AC: 0 AN: 595

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 113

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 25457

Other (OTH) AF: 0.00 AC: 0 AN: 564

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:1

Jul 31, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.48
PhyloP100		-0.80
PromoterAI		0.037	Neutral

Splicing

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

Other links and lift over

dbSNP: rs13440710; hg19: chrX-110987999;