chr9-137087032-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_016219.5(MAN1B1):āc.33T>Cā(p.Ala11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,602,436 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 34)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
MAN1B1
NM_016219.5 synonymous
NM_016219.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.154
Genes affected
MAN1B1 (HGNC:6823): (mannosidase alpha class 1B member 1) This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause autosomal-recessive intellectual disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Dec 2011]
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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=-0.85).
BP6
Variant 9-137087032-T-C is Benign according to our data. Variant chr9-137087032-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1731058.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.154 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAN1B1 | NM_016219.5 | c.33T>C | p.Ala11= | synonymous_variant | 1/13 | ENST00000371589.9 | |
MAN1B1 | XM_006716945.5 | c.33T>C | p.Ala11= | synonymous_variant | 1/12 | ||
MAN1B1 | NR_045720.2 | n.48T>C | non_coding_transcript_exon_variant | 1/13 | |||
MAN1B1 | NR_045721.2 | n.48T>C | non_coding_transcript_exon_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAN1B1 | ENST00000371589.9 | c.33T>C | p.Ala11= | synonymous_variant | 1/13 | 1 | NM_016219.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000224 AC: 5AN: 223198Hom.: 0 AF XY: 0.00000824 AC XY: 1AN XY: 121422
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GnomAD4 exome AF: 0.00000552 AC: 8AN: 1450284Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2AN XY: 720418
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 23, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at