rs12921879

Variant names:

• chr16-5078856-G-A
• rs12921879
• NM_019109.5:c.840G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-5078856-G-A
• chr16-5078856-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_019109.5(ALG1):​c.840G>A​(p.Leu280Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L280L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG1 NM_019109.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802
• Publications: 6 publications found

Genes affected

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ALG1 Gene-Disease associations (from GenCC):

• ALG1-congenital disorder of glycosylation

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.802 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019109.5. 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
	ALG1	NM_019109.5	MANE Select	c.840G>A	p.Leu280Leu	synonymous	Exon 7 of 13	NP_061982.3
	ALG1	NM_001438123.1		c.840G>A	p.Leu280Leu	synonymous	Exon 7 of 12	NP_001425052.1	A0A804HJL6
	ALG1	NM_001330504.2		c.507G>A	p.Leu169Leu	synonymous	Exon 7 of 13	NP_001317433.1	Q9BT22-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1	ENST00000262374.10	TSL:1 MANE Select	c.840G>A	p.Leu280Leu	synonymous	Exon 7 of 13	ENSP00000262374.5	Q9BT22-1
	ALG1	ENST00000588623.5	TSL:1	c.507G>A	p.Leu169Leu	synonymous	Exon 8 of 14	ENSP00000468118.1	Q9BT22-2
	ALG1	ENST00000591822.5	TSL:1	n.*741G>A		non_coding_transcript_exon	Exon 7 of 13	ENSP00000467865.1	K7EQK1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 61

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.2
DANN	Benign	0.85
PhyloP100		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12921879; hg19: chr16-5128857;