22-49903386-CCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024105.4(ALG12):c.*450_*451del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 457,934 control chromosomes in the GnomAD database, including 2,402 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (583 hom., cov: 31)
  • Exomes 𝑓: 0.10 (1819 hom.)
• Consequence: ALG12 NM_024105.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

Genes affected

ALG12 (HGNC:19358): (ALG12 alpha-1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-49903386-CCT-C is Benign according to our data. Variant chr22-49903386-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 342032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG12	NM_024105.4	c.*450_*451del		3_prime_UTR_variant	10/10	ENST00000330817.11
ALG12	XM_017028936.2	c.1238+791_1238+792del		intron_variant
ALG12	XM_017028937.2	c.1238+791_1238+792del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG12	ENST00000330817.11	c.*450_*451del		3_prime_UTR_variant	10/10	1	NM_024105.4	P1
	ENST00000610245.1	n.1160_1161del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11949 AN: 152140 Hom.: 583 Cov.: 31

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0664

GnomAD3 exomes AF: 0.0925 AC: 12704 AN: 137288 Hom.: 648 AF XY: 0.0967 AC XY: 7196 AN XY: 74424

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.0682

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0340

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0870

GnomAD4 exome AF: 0.103 AC: 31496 AN: 305678 Hom.: 1819 AF XY: 0.107 AC XY: 18633 AN XY: 173992

Gnomad4 AFR exome AF: 0.0182

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.0363

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0937

GnomAD4 genome AF: 0.0785 AC: 11950 AN: 152256 Hom.: 583 Cov.: 31 AF XY: 0.0781 AC XY: 5812 AN XY: 74442

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0657

Alfa AF: 0.0980 Hom.: 153

Bravo AF: 0.0704

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs16445; hg19: chr22-50297034;