3-51389023-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_006010.6(MANF):c.483C>T(p.Ile161Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,612,148 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0018 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 194 hom. )
Consequence
MANF
NM_006010.6 synonymous
NM_006010.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.599
Genes affected
MANF (HGNC:15461): (mesencephalic astrocyte derived neurotrophic factor) The protein encoded by this gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 3-51389023-C-T is Benign according to our data. Variant chr3-51389023-C-T is described in ClinVar as [Benign]. Clinvar id is 733337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.599 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00182 AC: 277AN: 152198Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.00657 AC: 1615AN: 245802Hom.: 61 AF XY: 0.00908 AC XY: 1212AN XY: 133446
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GnomAD4 exome AF: 0.00326 AC: 4758AN: 1459832Hom.: 194 Cov.: 31 AF XY: 0.00478 AC XY: 3469AN XY: 726010
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GnomAD4 genome AF: 0.00183 AC: 278AN: 152316Hom.: 6 Cov.: 33 AF XY: 0.00286 AC XY: 213AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Apr 07, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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