3-184242589-G-T

Variant names:

• chr3-184242589-G-T
• rs573414976
• NM_005787.6:c.1242C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005787.6(ALG3):​c.1242C>A​(p.Ala414Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A414A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG3 NM_005787.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 0 publications found

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]

VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.114).
• BP7: Synonymous conserved (PhyloP=-0.629 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005787.6. 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
	ALG3	NM_005787.6	MANE Select	c.1242C>A	p.Ala414Ala	synonymous	Exon 9 of 9	NP_005778.1	Q92685-1
	ALG3	NM_001006941.2		c.1098C>A	p.Ala366Ala	synonymous	Exon 9 of 9	NP_001006942.1	Q92685-2
	ALG3	NR_024533.1		n.1173C>A		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG3	ENST00000397676.8	TSL:1 MANE Select	c.1242C>A	p.Ala414Ala	synonymous	Exon 9 of 9	ENSP00000380793.3	Q92685-1
	ALG3	ENST00000445626.6	TSL:1	c.1098C>A	p.Ala366Ala	synonymous	Exon 9 of 9	ENSP00000402744.2	Q92685-2
	ALG3	ENST00000411922.5	TSL:1	n.*818C>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000394917.1	F8WE30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.23
DANN	Benign	0.70
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs573414976; hg19: chr3-183960377;