chr13-52018792-G-A

Position:

• chr13-52018792-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001004127.3(ALG11):​c.45-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 845,064 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (15 hom.)
• Consequence: ALG11 NM_001004127.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0750

Genes affected

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-52018792-G-A is Benign according to our data. Variant chr13-52018792-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00526 (801/152210) while in subpopulation NFE AF= 0.00778 (529/68006). AF 95% confidence interval is 0.00723. There are 6 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3	c.45-121G>A		intron_variant		ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3	n.65+6330G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2	c.45-121G>A		intron_variant		1	NM_001004127.3	ENSP00000430236	P4

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 801 AN: 152092 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00684 AC: 4741 AN: 692854 Hom.: 15 AF XY: 0.00669 AC XY: 2434 AN XY: 363596

Gnomad4 AFR exome AF: 0.00113

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00708

Gnomad4 EAS exome AF: 0.0000310

Gnomad4 SAS exome AF: 0.00375

Gnomad4 FIN exome AF: 0.0122

Gnomad4 NFE exome AF: 0.00782

Gnomad4 OTH exome AF: 0.00535

GnomAD4 genome AF: 0.00526 AC: 801 AN: 152210 Hom.: 6 Cov.: 32 AF XY: 0.00556 AC XY: 414 AN XY: 74430

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00356 Hom.: 1

Bravo AF: 0.00424

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs192248956; hg19: chr13-52592928;