rs765948340

Variant names:

• chrX-111708952-CTCT-C
• rs765948340
• NM_001099922.3:c.751-8_751-6delCTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.751-8_751-6delCTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000906 in 1,147,559 control chromosomes in the GnomAD database, including 2 homozygotes. There are 19 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000093 (2 hom. 19 hem.)
• Consequence: ALG13 NM_001099922.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.90
• 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-AS1 (HGNC:41277): (ALG13 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant X-111708952-CTCT-C is Benign according to our data. Variant chrX-111708952-CTCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412615.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 = 0.0000715 (8/111964) while in subpopulation EAS AF = 0.000839 (3/3576). AF 95% confidence interval is 0.000228. 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 Homozygotes in GnomAdExome4 at 2 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.751-8_751-6delCTT		splice_region intron	N/A	NP_001093392.1
	ALG13	NM_001257231.2		c.517-8_517-6delCTT		splice_region intron	N/A	NP_001244160.1
	ALG13	NM_001324292.2		c.751-8_751-6delCTT		splice_region intron	N/A	NP_001311221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.751-12_751-10delTCT		intron	N/A	ENSP00000378260.3
	ALG13	ENST00000927365.1		c.751-12_751-10delTCT		intron	N/A	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.751-12_751-10delTCT		intron	N/A	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.0000715 AC: 8 AN: 111964 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000378

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000839

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000744 AC: 10 AN: 134319 AF XY: 0.0000499

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000574

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.000838

GnomAD4 exome AF: 0.0000927 AC: 96 AN: 1035595 Hom.: 2 AF XY: 0.0000597 AC XY: 19 AN XY: 318299

African (AFR) AF: 0.00 AC: 0 AN: 25099

American (AMR) AF: 0.00 AC: 0 AN: 30532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18112

East Asian (EAS) AF: 0.000498 AC: 14 AN: 28138

South Asian (SAS) AF: 0.00 AC: 0 AN: 49587

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3970

European-Non Finnish (NFE) AF: 0.00000626 AC: 5 AN: 798969

Other (OTH) AF: 0.00177 AC: 77 AN: 43470

GnomAD4 genome AF: 0.0000715 AC: 8 AN: 111964 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34164

African (AFR) AF: 0.00 AC: 0 AN: 30769

American (AMR) AF: 0.000378 AC: 4 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.000839 AC: 3 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6079

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53186

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.000478 Hom.: 4

Bravo AF: 0.000159

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
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: rs765948340; hg19: chrX-110952180;