chrX-111708970-T-C

Variant names:

• chrX-111708970-T-C
• rs915629293
• NM_001099922.3:c.756T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001099922.3(ALG13):​c.756T>C​(p.Phe252Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,065,037 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000056 (0 hom. 2 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-111708970-T-C is Benign according to our data. Variant chrX-111708970-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1615144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.756T>C	p.Phe252Phe	synonymous_variant	Exon 5 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.756T>C	p.Phe252Phe	synonymous_variant	Exon 5 of 27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000685 AC: 1 AN: 145969 AF XY: 0.0000230

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000563 AC: 6 AN: 1065037 Hom.: 0 Cov.: 24 AF XY: 0.00000591 AC XY: 2 AN XY: 338381

African (AFR) AF: 0.00 AC: 0 AN: 25769

American (AMR) AF: 0.00 AC: 0 AN: 32354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18499

East Asian (EAS) AF: 0.00 AC: 0 AN: 28962

South Asian (SAS) AF: 0.000118 AC: 6 AN: 50845

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 821498

Other (OTH) AF: 0.00 AC: 0 AN: 44568

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:1

Aug 15, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Other links and lift over

dbSNP: rs915629293; hg19: chrX-110952198;