22-49903347-C-T

Variant names:

• chr22-49903347-C-T
• rs886057612
• NM_024105.4:c.*491G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024105.4(ALG12):​c.*491G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000327 in 305,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: ALG12 NM_024105.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• 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: ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000273192 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024105.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	NM_024105.4	MANE Select	c.*491G>A		3_prime_UTR	Exon 10 of 10	NP_077010.1	Q9BV10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	ENST00000330817.11	TSL:1 MANE Select	c.*491G>A		3_prime_UTR	Exon 10 of 10	ENSP00000333813.5	Q9BV10
	ALG12	ENST00000905517.1		c.*491G>A		3_prime_UTR	Exon 10 of 10	ENSP00000575576.1
	ALG12	ENST00000905518.1		c.*491G>A		3_prime_UTR	Exon 10 of 10	ENSP00000575577.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000327 AC: 1 AN: 305448 Hom.: 0 Cov.: 0 AF XY: 0.00000575 AC XY: 1 AN XY: 173840

African (AFR) AF: 0.00 AC: 0 AN: 8666

American (AMR) AF: 0.00 AC: 0 AN: 27268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10868

East Asian (EAS) AF: 0.00 AC: 0 AN: 9378

South Asian (SAS) AF: 0.00 AC: 0 AN: 59712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2218

European-Non Finnish (NFE) AF: 0.00000624 AC: 1 AN: 160146

Other (OTH) AF: 0.00 AC: 0 AN: 14288

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.37
PhyloP100		-0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs886057612; hg19: chr22-50296995;