rs11547261
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021971.4(GMPPB):c.330C>T(p.Asp110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,613,370 control chromosomes in the GnomAD database, including 334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 16 hom., cov: 33)
Exomes 𝑓: 0.019 ( 318 hom. )
Consequence
GMPPB
NM_021971.4 synonymous
NM_021971.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.18
Genes affected
GMPPB (HGNC:22932): (GDP-mannose pyrophosphorylase B) This gene is thought to encode a GDP-mannose pyrophosphorylase. The encoded protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a reaction involved in the production of N-linked oligosaccharides. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 3-49723044-G-A is Benign according to our data. Variant chr3-49723044-G-A is described in ClinVar as [Benign]. Clinvar id is 260284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49723044-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.18 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1812/152280) while in subpopulation NFE AF= 0.02 (1363/68020). AF 95% confidence interval is 0.0192. There are 16 homozygotes in gnomad4. There are 854 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMPPB | NM_021971.4 | c.330C>T | p.Asp110= | synonymous_variant | 4/9 | ENST00000308388.7 | |
GMPPB | NM_013334.4 | c.330C>T | p.Asp110= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMPPB | ENST00000308388.7 | c.330C>T | p.Asp110= | synonymous_variant | 4/9 | 1 | NM_021971.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0119 AC: 1812AN: 152162Hom.: 16 Cov.: 33
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GnomAD3 exomes AF: 0.0131 AC: 3294AN: 251144Hom.: 32 AF XY: 0.0134 AC XY: 1824AN XY: 135806
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GnomAD4 exome AF: 0.0186 AC: 27210AN: 1461090Hom.: 318 Cov.: 31 AF XY: 0.0183 AC XY: 13310AN XY: 726898
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GnomAD4 genome ? AF: 0.0119 AC: 1812AN: 152280Hom.: 16 Cov.: 33 AF XY: 0.0115 AC XY: 854AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14;C3809221:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14;C4518000:Autosomal recessive limb-girdle muscular dystrophy type 2T Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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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