rs35400794

Variant names:

• chr16-5072071-G-GGTCT
• rs35400794
• NM_019109.5:c.208+16_208+19dupTCTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_019109.5(ALG1):​c.208+16_208+19dupTCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,557,476 control chromosomes in the GnomAD database, including 250,491 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23328 hom., cov: 0)
  • Exomes 𝑓: 0.57 (227163 hom.)
• Consequence: ALG1 NM_019109.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.422
• 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-5072071-G-GGTCT is Benign according to our data. Variant chr16-5072071-G-GGTCT is described in ClinVar as Benign. ClinVar VariationId is 95935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

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.208+16_208+19dupTCTG		intron	N/A	NP_061982.3
	ALG1	NM_001438123.1		c.208+16_208+19dupTCTG		intron	N/A	NP_001425052.1	A0A804HJL6
	ALG1	NM_001330504.2		c.-358_-357insGTCT		upstream_gene	N/A	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.208+16_208+19dupTCTG		intron	N/A	ENSP00000262374.5	Q9BT22-1
	ALG1	ENST00000588623.5	TSL:1	c.-125-878_-125-875dupTCTG		intron	N/A	ENSP00000468118.1	Q9BT22-2
	ALG1	ENST00000591822.5	TSL:1	n.224_227dupTCTG		non_coding_transcript_exon	Exon 1 of 13	ENSP00000467865.1	K7EQK1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83676 AN: 151190 Hom.: 23311 Cov.: 0

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.525

GnomAD2 exomes AF: 0.558 AC: 87400 AN: 156722 AF XY: 0.569

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.566 AC: 795844 AN: 1406168 Hom.: 227163 Cov.: 81 AF XY: 0.569 AC XY: 395389 AN XY: 694410

African (AFR) AF: 0.560 AC: 17968 AN: 32084

American (AMR) AF: 0.426 AC: 15730 AN: 36934

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11980 AN: 25290

East Asian (EAS) AF: 0.646 AC: 23543 AN: 36432

South Asian (SAS) AF: 0.681 AC: 54471 AN: 80042

European-Finnish (FIN) AF: 0.582 AC: 28267 AN: 48554

Middle Eastern (MID) AF: 0.515 AC: 2935 AN: 5704

European-Non Finnish (NFE) AF: 0.561 AC: 607804 AN: 1082852

Other (OTH) AF: 0.569 AC: 33146 AN: 58276

GnomAD4 genome AF: 0.553 AC: 83730 AN: 151308 Hom.: 23328 Cov.: 0 AF XY: 0.558 AC XY: 41254 AN XY: 73920

African (AFR) AF: 0.545 AC: 22502 AN: 41270

American (AMR) AF: 0.468 AC: 7139 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1619 AN: 3462

East Asian (EAS) AF: 0.675 AC: 3408 AN: 5046

South Asian (SAS) AF: 0.697 AC: 3344 AN: 4798

European-Finnish (FIN) AF: 0.593 AC: 6198 AN: 10458

Middle Eastern (MID) AF: 0.510 AC: 148 AN: 290

European-Non Finnish (NFE) AF: 0.558 AC: 37799 AN: 67726

Other (OTH) AF: 0.530 AC: 1117 AN: 2106

Alfa AF: 0.542 Hom.: 4649

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	ALG1-congenital disorder of glycosylation (3)
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35400794; hg19: chr16-5122072;