rs1060500008

Variant names:

• chrX-111708095-C-T
• rs1060500008
• NM_001099922.3:c.452C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099922.3(ALG13):​c.452C>T​(p.Ala151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,682 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A151A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.52
• Publications: 3 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-AS1 (HGNC:41277): (ALG13 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050131172).

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.452C>T	p.Ala151Val	missense	Exon 4 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.218C>T	p.Ala73Val	missense	Exon 4 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.452C>T	p.Ala151Val	missense	Exon 4 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.452C>T	p.Ala151Val	missense	Exon 4 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.452C>T	p.Ala151Val	missense	Exon 4 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.452C>T	p.Ala151Val	missense	Exon 4 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111837 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 9.11e-7 AC: 1 AN: 1097682 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363126

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54077

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841782

Other (OTH) AF: 0.00 AC: 0 AN: 46066

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000894 AC: 1 AN: 111837 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 33989

African (AFR) AF: 0.0000325 AC: 1 AN: 30735

American (AMR) AF: 0.00 AC: 0 AN: 10556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.00 AC: 0 AN: 2680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6051

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53201

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 36 (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.26
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.040
Sift	Benign	0.047	D
Sift4G	Uncertain	0.050	T
Polyphen		0.0030	B
Vest4		0.048
MutPred		0.36		Loss of disorder (P = 0.0437)
MVP		0.44
MPC		0.17
ClinPred		0.046	T
GERP RS		-4.8
Varity_R		0.049
gMVP		0.19
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1060500008; hg19: chrX-110951323; COSMIC: COSV52637744;