5-109713524-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002372.4(MAN2A1):āc.140A>Cā(p.Gln47Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,451,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MAN2A1
NM_002372.4 missense
NM_002372.4 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 7.42
Genes affected
MAN2A1 (HGNC:6824): (mannosidase alpha class 2A member 1) This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.863
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAN2A1 | NM_002372.4 | c.140A>C | p.Gln47Pro | missense_variant | 2/22 | ENST00000261483.5 | NP_002363.2 | |
MAN2A1 | XM_011543395.4 | c.140A>C | p.Gln47Pro | missense_variant | 2/17 | XP_011541697.1 | ||
MAN2A1 | XM_017009472.2 | c.-8A>C | 5_prime_UTR_variant | 2/22 | XP_016864961.1 | |||
MAN2A1 | XR_007058604.1 | n.631A>C | non_coding_transcript_exon_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAN2A1 | ENST00000261483.5 | c.140A>C | p.Gln47Pro | missense_variant | 2/22 | 1 | NM_002372.4 | ENSP00000261483.4 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152200Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome AF: 0.00000482 AC: 7AN: 1451316Hom.: 0 Cov.: 33 AF XY: 0.00000417 AC XY: 3AN XY: 720228
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2023 | The c.140A>C (p.Q47P) alteration is located in exon 2 (coding exon 2) of the MAN2A1 gene. This alteration results from a A to C substitution at nucleotide position 140, causing the glutamine (Q) at amino acid position 47 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of helix (P = 0.0237);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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