rs763318921

Variant names:

• chrX-111708022-C-T
• rs763318921
• NM_001099922.3:c.384-5C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.384-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,194,243 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000068 (0 hom. 17 hem.)
• Consequence: ALG13 NM_001099922.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002313
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.71
• Publications: 1 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-111708022-C-T is Benign according to our data. Variant chrX-111708022-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000985 (11/111660) while in subpopulation EAS AF = 0.00312 (11/3527). AF 95% confidence interval is 0.00175. There are 0 homozygotes in GnomAd4. There are 0 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 17 XL gene

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.384-5C>T		splice_region intron	N/A	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.150-5C>T		splice_region intron	N/A	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.384-5C>T		splice_region intron	N/A	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.384-5C>T		splice_region intron	N/A	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.384-5C>T		splice_region intron	N/A	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.384-5C>T		splice_region intron	N/A	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 11 AN: 111605 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00311

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

GnomAD2 exomes AF: 0.000318 AC: 51 AN: 160480 AF XY: 0.000197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000509

GnomAD4 exome AF: 0.0000684 AC: 74 AN: 1082583 Hom.: 0 Cov.: 31 AF XY: 0.0000483 AC XY: 17 AN XY: 351821

African (AFR) AF: 0.00 AC: 0 AN: 25944

American (AMR) AF: 0.00 AC: 0 AN: 33771

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18610

East Asian (EAS) AF: 0.00167 AC: 50 AN: 29962

South Asian (SAS) AF: 0.00 AC: 0 AN: 52151

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39825

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3921

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833077

Other (OTH) AF: 0.000530 AC: 24 AN: 45322

GnomAD4 genome AF: 0.0000985 AC: 11 AN: 111660 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33844

African (AFR) AF: 0.00 AC: 0 AN: 30772

American (AMR) AF: 0.00 AC: 0 AN: 10494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00312 AC: 11 AN: 3527

South Asian (SAS) AF: 0.00 AC: 0 AN: 2652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6033

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53119

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Developmental and epileptic encephalopathy, 36 (2)
-	-	1	ALG13-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0

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

Other links and lift over

dbSNP: rs763318921; hg19: chrX-110951250;