16-5078854-C-T

Variant names:

• chr16-5078854-C-T
• NM_019109.5:c.838C>T
• ALG1 p.Leu280Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_019109.5(ALG1):​c.838C>T​(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. Variant has been reported in ClinVar as Likely benign (★). 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: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.582
• Publications: 0 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: Ambry Genetics, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000260882 (HGNC:):

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=-0.43).
• BP6: Variant 16-5078854-C-T is Benign according to our data. Variant chr16-5078854-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3632136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.582 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.838C>T	p.Leu280Leu	synonymous	Exon 7 of 13	NP_061982.3
	ALG1	NM_001438123.1		c.838C>T	p.Leu280Leu	synonymous	Exon 7 of 12	NP_001425052.1	A0A804HJL6
	ALG1	NM_001330504.2		c.505C>T	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.838C>T	p.Leu280Leu	synonymous	Exon 7 of 13	ENSP00000262374.5	Q9BT22-1
	ALG1	ENST00000588623.5	TSL:1	c.505C>T	p.Leu169Leu	synonymous	Exon 8 of 14	ENSP00000468118.1	Q9BT22-2
	ALG1	ENST00000591822.5	TSL:1	n.*739C>T		non_coding_transcript_exon	Exon 7 of 13	ENSP00000467865.1	K7EQK1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	ALG1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.9
DANN	Benign	0.85
PhyloP100		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-5128855;