Variant rs2233465 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005787.6(ALG3):c.727-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,562,822 control chromosomes in the GnomAD database, including 1,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 74 hom., cov: 32)

Exomes 𝑓: 0.034 ( 944 hom. )

Consequence

ALG3
NM_005787.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.144

Variant links:

Genes affected

ALG3 (HGNC:23056): (ALG3 alpha-1,3- mannosyltransferase) This gene encodes a member of the ALG3 family. The encoded protein catalyses the addition of the first dol-P-Man derived mannose in an alpha 1,3 linkage to Man5GlcNAc2-PP-Dol. Defects in this gene have been associated with congenital disorder of glycosylation type Id (CDG-Id) characterized by abnormal N-glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ALG3 links:

ALG3 (HGNC:):

ALG3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-184244046-A-G is Benign according to our data. Variant chr3-184244046-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4004/152274) while in subpopulation NFE AF= 0.0411 (2792/68000). AF 95% confidence interval is 0.0398. There are 74 homozygotes in gnomad4. There are 1826 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALG3	NM_005787.6 linkuse as main transcript	c.727-50T>C	intron_variant	ENST00000397676.8	NP_005778.1	Q92685-1
ALG3	NM_001006941.2 linkuse as main transcript	c.583-50T>C	intron_variant		NP_001006942.1	Q92685-2
ALG3	NR_024533.1 linkuse as main transcript	n.658-50T>C	intron_variant
ALG3	NR_024534.1 linkuse as main transcript	n.721-50T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG3	ENST00000397676.8 linkuse as main transcript	c.727-50T>C		intron_variant		1	NM_005787.6	ENSP00000380793.3		Q92685-1

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

4003

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0264

AC:

6106

AN:

231000

Hom.:

AF XY:

0.0267

AC XY:

3351

AN XY:

125610

show subpopulations

Gnomad AFR exome

AF:

0.00564

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0483

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00579

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0369

GnomAD4 exome

AF:

0.0343

AC:

48360

AN:

1410548

Hom.:

944

Cov.:

AF XY:

0.0336

AC XY:

23491

AN XY:

699694

show subpopulations

Gnomad4 AFR exome

AF:

0.00557

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0456

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0263

AC:

4004

AN:

152274

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1826

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00642

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0217

Gnomad4 NFE

AF:

0.0411

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0361

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 17, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over