22-49903880-C-T

Variant names:

• chr22-49903880-C-T
• rs147000290
• NM_024105.4:c.1425G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_024105.4(ALG12):​c.1425G>A​(p.Gln475Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG12 NM_024105.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.989
• Publications: 0 publications found

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]

ALG12 Gene-Disease associations (from GenCC):

• ALG12-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ENSG00000273192 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-49903880-C-T is Benign according to our data. Variant chr22-49903880-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2035870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.989 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG12	NM_024105.4	c.1425G>A	p.Gln475Gln	synonymous_variant	Exon 10 of 10	ENST00000330817.11	NP_077010.1
ALG12	XM_017028936.2	c.1238+299G>A		intron_variant	Intron 9 of 9		XP_016884425.1
ALG12	XM_017028937.2	c.1238+299G>A		intron_variant	Intron 9 of 10		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11	c.1425G>A	p.Gln475Gln	synonymous_variant	Exon 10 of 10	1	NM_024105.4	ENSP00000333813.5
ENSG00000273192	ENST00000610245.1	n.1653C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ALG12	ENST00000486602.1	c.444-1G>A		splice_acceptor_variant, intron_variant	Intron 3 of 3	3		ENSP00000420630.1
ALG12	ENST00000492791.1	n.*244G>A		downstream_gene_variant		3		ENSP00000417387.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ALG12-congenital disorder of glycosylation Benign:1

Oct 17, 2022

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	-0.47
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147000290; hg19: chr22-50297528;