chr3-184242577-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_005787.6(ALG3):c.1254G>A(p.Leu418=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,607,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
ALG3
NM_005787.6 synonymous
NM_005787.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.811
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 3-184242577-C-T is Benign according to our data. Variant chr3-184242577-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2151586.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.811 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG3 | NM_005787.6 | c.1254G>A | p.Leu418= | synonymous_variant | 9/9 | ENST00000397676.8 | |
ALG3 | NM_001006941.2 | c.1110G>A | p.Leu370= | synonymous_variant | 9/9 | ||
ALG3 | NR_024533.1 | n.1185G>A | non_coding_transcript_exon_variant | 8/8 | |||
ALG3 | NR_024534.1 | n.1248G>A | non_coding_transcript_exon_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG3 | ENST00000397676.8 | c.1254G>A | p.Leu418= | synonymous_variant | 9/9 | 1 | NM_005787.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000410 AC: 1AN: 243868Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132526
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GnomAD4 exome AF: 0.0000131 AC: 19AN: 1454972Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8AN XY: 722688
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ALG3-congenital disorder of glycosylation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at