X-111685091-A-T

Variant names:

• chrX-111685091-A-T
• rs145518377
• NM_001099922.3:c.371A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099922.3(ALG13):​c.371A>T​(p.Tyr124Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,266 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y124C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39778328).

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.371A>T	p.Tyr124Phe	missense	Exon 3 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.137A>T	p.Tyr46Phe	missense	Exon 3 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.371A>T	p.Tyr124Phe	missense	Exon 3 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.371A>T	p.Tyr124Phe	missense	Exon 3 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000371979.7	TSL:1	c.371A>T	p.Tyr124Phe	missense	Exon 3 of 4	ENSP00000361047.3	Q9NP73-2
	ALG13	ENST00000927365.1		c.371A>T	p.Tyr124Phe	missense	Exon 3 of 27	ENSP00000597424.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095266 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360844

African (AFR) AF: 0.00 AC: 0 AN: 26252

American (AMR) AF: 0.00 AC: 0 AN: 34474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19272

East Asian (EAS) AF: 0.00 AC: 0 AN: 30145

South Asian (SAS) AF: 0.00 AC: 0 AN: 53457

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40493

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841061

Other (OTH) AF: 0.00 AC: 0 AN: 45989

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.33	T
PhyloP100		3.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.28
Sift	Benign	0.036	D
Sift4G	Benign	0.28	T
Polyphen		0.27	B
Vest4		0.54
MutPred		0.43		Loss of sheet (P = 0.1398)
MVP		0.80
MPC		0.55
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.34
gMVP		0.13
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs145518377; hg19: chrX-110928319;