rs35400794

Positions:

• chr16-5072071-G-GGTCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_019109.5(ALG1):​c.208+16_208+19dup 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:6
• Conservation: PhyloP100: -0.422

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG1	NM_019109.5	c.208+16_208+19dup		intron_variant		ENST00000262374.10
ALG1	XM_017023457.3	c.208+16_208+19dup		intron_variant
ALG1	XR_007064892.1	n.215+16_215+19dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG1	ENST00000262374.10	c.208+16_208+19dup		intron_variant		1	NM_019109.5	P1

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

GnomAD3 exomes AF: 0.558 AC: 87400 AN: 156722 Hom.: 25129 AF XY: 0.569 AC XY: 48038 AN XY: 84424

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 SAS exome AF: 0.682

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

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.569

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.530

Alfa AF: 0.542 Hom.: 4649

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ALG1-congenital disorder of glycosylation Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 18, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 06, 2014	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35400794; hg19: chr16-5122072;