NM_001099922.3:c.3039A>C

Variant names:

• chrX-111757653-A-C
• NM_001099922.3:c.3039A>C
• ALG13 p.Val1013Val

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001099922.3(ALG13):​c.3039A>C​(p.Val1013Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V1013V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 0 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.033 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.3039A>C	p.Val1013Val	synonymous	Exon 26 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2805A>C	p.Val935Val	synonymous	Exon 26 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2802A>C	p.Val934Val	synonymous	Exon 25 of 26	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.3039A>C	p.Val1013Val	synonymous	Exon 26 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.3015A>C	p.Val1005Val	synonymous	Exon 26 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2865A>C	p.Val955Val	synonymous	Exon 24 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.033

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.

Other links and lift over

hg19: chrX-111000881;