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GeneBe

8-120451042-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022045.5(MTBP):c.239T>C(p.Phe80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MTBP
NM_022045.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTBPNM_022045.5 linkuse as main transcriptc.239T>C p.Phe80Ser missense_variant 3/22 ENST00000305949.6
MTBPXM_011516962.3 linkuse as main transcriptc.239T>C p.Phe80Ser missense_variant 3/18
MTBPXM_011516963.3 linkuse as main transcriptc.239T>C p.Phe80Ser missense_variant 3/14
MTBPXR_928318.3 linkuse as main transcriptn.291T>C non_coding_transcript_exon_variant 3/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTBPENST00000305949.6 linkuse as main transcriptc.239T>C p.Phe80Ser missense_variant 3/221 NM_022045.5 P1Q96DY7-1
MTBPENST00000456899.6 linkuse as main transcriptn.310T>C non_coding_transcript_exon_variant 3/33
MTBPENST00000522308.1 linkuse as main transcriptn.288T>C non_coding_transcript_exon_variant 3/42
MTBPENST00000523373.5 linkuse as main transcriptc.239T>C p.Phe80Ser missense_variant, NMD_transcript_variant 3/115 Q96DY7-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJun 30, 2023The c.239T>C (p.F80S) alteration is located in exon 3 (coding exon 3) of the MTBP gene. This alteration results from a T to C substitution at nucleotide position 239, causing the phenylalanine (F) at amino acid position 80 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.32
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.41
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.80
D
MetaSVM
Benign
-0.36
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
0.97
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.2
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.99
D
Vest4
0.84
MutPred
0.47
Gain of disorder (P = 0.0126);
MVP
0.59
MPC
0.84
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.55
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-121463282; API