chr5-109774877-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002372.4(MAN2A1):c.1286A>T(p.Tyr429Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,611,812 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
MAN2A1
NM_002372.4 missense
NM_002372.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.85
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08406305).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAN2A1 | NM_002372.4 | c.1286A>T | p.Tyr429Phe | missense_variant | 8/22 | ENST00000261483.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAN2A1 | ENST00000261483.5 | c.1286A>T | p.Tyr429Phe | missense_variant | 8/22 | 1 | NM_002372.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000244 AC: 37AN: 151838Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000797 AC: 20AN: 250790Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135562
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1459974Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726352
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GnomAD4 genome AF: 0.000244 AC: 37AN: 151838Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17AN XY: 74122
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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 | Dec 07, 2021 | The c.1286A>T (p.Y429F) alteration is located in exon 8 (coding exon 8) of the MAN2A1 gene. This alteration results from a A to T substitution at nucleotide position 1286, causing the tyrosine (Y) at amino acid position 429 to be replaced by a phenylalanine (F). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
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