16-5071691-C-G

Variant names:

• chr16-5071691-C-G
• rs17523310
• ENST00000588623.5:c.-125-1260C>G

Variant summary

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

The ENST00000588623.5(ALG1):​c.-125-1260C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,074,304 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: 9.3e-7 (0 hom.)
• Consequence: ALG1 ENST00000588623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000588623.5. 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.-159C>G		upstream_gene	N/A	NP_061982.3
	ALG1	NM_001438123.1		c.-159C>G		upstream_gene	N/A	NP_001425052.1	A0A804HJL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1	ENST00000588623.5	TSL:1	c.-125-1260C>G		intron	N/A	ENSP00000468118.1	Q9BT22-2
	ALG1	ENST00000682985.1		c.-99-3697C>G		intron	N/A	ENSP00000507598.1	A0A804HJQ1
	ALG1	ENST00000682327.1		c.-99-3697C>G		intron	N/A	ENSP00000507058.1	A0A804HIG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1074304 Hom.: 0 AF XY: 0.00000186 AC XY: 1 AN XY: 538984

African (AFR) AF: 0.00 AC: 0 AN: 25286

American (AMR) AF: 0.00 AC: 0 AN: 31348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20670

East Asian (EAS) AF: 0.00 AC: 0 AN: 34258

South Asian (SAS) AF: 0.00 AC: 0 AN: 67050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3362

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 813068

Other (OTH) AF: 0.00 AC: 0 AN: 47212

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.39
PhyloP100		0.44
PromoterAI		0.0042	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17523310; hg19: chr16-5121692;