rs78916708

Variant names:

• chr22-49910421-G-A
• rs78916708
• NM_024105.4:c.469+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-49910421-G-A
• chr22-49910421-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024105.4(ALG12):​c.469+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,612,618 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (22 hom., cov: 33)
  • Exomes 𝑓: 0.018 (286 hom.)
• Consequence: ALG12 NM_024105.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.453

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=-0.85).
• BP6: Variant 22-49910421-G-A is Benign according to our data. Variant chr22-49910421-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261686.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 = 0.0134 (2047/152358) while in subpopulation EAS AF= 0.0248 (129/5192). AF 95% confidence interval is 0.0214. There are 22 homozygotes in gnomad4. There are 1026 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG12	NM_024105.4	c.469+13C>T		intron_variant	Intron 4 of 9	ENST00000330817.11	NP_077010.1
ALG12	XM_017028936.2	c.469+13C>T		intron_variant	Intron 4 of 9		XP_016884425.1
ALG12	XM_017028937.2	c.469+13C>T		intron_variant	Intron 4 of 10		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11	c.469+13C>T		intron_variant	Intron 4 of 9	1	NM_024105.4	ENSP00000333813.5

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2048 AN: 152240 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0160 AC: 3949 AN: 247344 Hom.: 46 AF XY: 0.0156 AC XY: 2097 AN XY: 134238

Gnomad AFR exome AF: 0.00282

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.00181

Gnomad EAS exome AF: 0.0229

Gnomad SAS exome AF: 0.00475

Gnomad FIN exome AF: 0.0303

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0204

GnomAD4 exome AF: 0.0182 AC: 26523 AN: 1460260 Hom.: 286 Cov.: 32 AF XY: 0.0177 AC XY: 12854 AN XY: 726388

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.0405

Gnomad4 SAS exome AF: 0.00515

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0190

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0134 AC: 2047 AN: 152358 Hom.: 22 Cov.: 33 AF XY: 0.0138 AC XY: 1026 AN XY: 74498

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0131 Hom.: 1

Bravo AF: 0.0118

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 20, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ALG12-congenital disorder of glycosylation Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.29
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78916708; hg19: chr22-50304069; COSMIC: COSV58206255; COSMIC: COSV58206255;