rs9616367

chr22-49909867-A-Cchr22-49909867-A-Gchr22-49909867-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024105.4(ALG12):c.664+27T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,612,502 control chromosomes in the GnomAD database, including 40,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4925 hom., cov: 34)
  • Exomes 𝑓: 0.21 (35131 hom.)
• Consequence: ALG12 NM_024105.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.923

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-49909867-A-C is Benign according to our data. Variant chr22-49909867-A-C is described in ClinVar as [Benign]. Clinvar id is 261687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG12	NM_024105.4	c.664+27T>G		intron_variant		ENST00000330817.11
ALG12	XM_017028936.2	c.664+27T>G		intron_variant
ALG12	XM_017028937.2	c.664+27T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG12	ENST00000330817.11	c.664+27T>G		intron_variant		1	NM_024105.4	P1
ALG12	ENST00000492791.1	c.195+27T>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36645 AN: 152210 Hom.: 4911 Cov.: 34

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.215 AC: 53840 AN: 250526 Hom.: 6931 AF XY: 0.225 AC XY: 30528 AN XY: 135520

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.0825

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.209 AC: 305269 AN: 1460174 Hom.: 35131 Cov.: 33 AF XY: 0.216 AC XY: 156578 AN XY: 726498

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.0918

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.241 AC: 36694 AN: 152328 Hom.: 4925 Cov.: 34 AF XY: 0.239 AC XY: 17787 AN XY: 74486

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.219

Alfa AF: 0.149 Hom.: 455

Bravo AF: 0.239

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.2
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9616367; hg19: chr22-50303515; COSMIC: COSV58206596; COSMIC: COSV58206596;