chr8-120453852-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_022045.5(MTBP):c.431A>G(p.Tyr144Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,572,622 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0080 ( 14 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 30 hom. )
Consequence
MTBP
NM_022045.5 missense
NM_022045.5 missense
Scores
11
7
Clinical Significance
Conservation
PhyloP100: 2.20
Genes affected
MTBP (HGNC:7417): (MDM2 binding protein) This gene encodes a protein that interacts with the oncoprotein mouse double minute 2. The encoded protein regulates progression through the cell cycle and may be involved in tumor formation. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010437548).
BP6
?
Variant 8-120453852-A-G is Benign according to our data. Variant chr8-120453852-A-G is described in ClinVar as [Benign]. Clinvar id is 774248.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1213/152202) while in subpopulation AFR AF= 0.0216 (898/41558). AF 95% confidence interval is 0.0204. There are 14 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTBP | NM_022045.5 | c.431A>G | p.Tyr144Cys | missense_variant | 5/22 | ENST00000305949.6 | |
MTBP | XM_011516962.3 | c.431A>G | p.Tyr144Cys | missense_variant | 5/18 | ||
MTBP | XM_011516963.3 | c.431A>G | p.Tyr144Cys | missense_variant | 5/14 | ||
MTBP | XR_928318.3 | n.483A>G | non_coding_transcript_exon_variant | 5/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTBP | ENST00000305949.6 | c.431A>G | p.Tyr144Cys | missense_variant | 5/22 | 1 | NM_022045.5 | P1 | |
MTBP | ENST00000523373.5 | c.431A>G | p.Tyr144Cys | missense_variant, NMD_transcript_variant | 5/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00795 AC: 1209AN: 152082Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00395 AC: 951AN: 240620Hom.: 5 AF XY: 0.00374 AC XY: 487AN XY: 130300
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GnomAD4 exome AF: 0.00248 AC: 3523AN: 1420420Hom.: 30 Cov.: 25 AF XY: 0.00255 AC XY: 1805AN XY: 707600
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GnomAD4 genome ? AF: 0.00797 AC: 1213AN: 152202Hom.: 14 Cov.: 32 AF XY: 0.00784 AC XY: 583AN XY: 74408
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ESP6500AA
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ExAC
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Asia WGS
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3464
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
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