8-120451267-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022045.5(MTBP):​c.370G>A​(p.Val124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
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]

Genome browser will be placed here

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=0.07496062).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTBPNM_022045.5 linkuse as main transcriptc.370G>A p.Val124Ile missense_variant 4/22 ENST00000305949.6 NP_071328.2 Q96DY7-1
MTBPXM_011516962.3 linkuse as main transcriptc.370G>A p.Val124Ile missense_variant 4/18 XP_011515264.1
MTBPXM_011516963.3 linkuse as main transcriptc.370G>A p.Val124Ile missense_variant 4/14 XP_011515265.1
MTBPXR_928318.3 linkuse as main transcriptn.422G>A non_coding_transcript_exon_variant 4/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTBPENST00000305949.6 linkuse as main transcriptc.370G>A p.Val124Ile missense_variant 4/221 NM_022045.5 ENSP00000303398.1 Q96DY7-1
MTBPENST00000456899.6 linkuse as main transcriptn.535G>A non_coding_transcript_exon_variant 3/33
MTBPENST00000522308.1 linkuse as main transcriptn.419G>A non_coding_transcript_exon_variant 4/42
MTBPENST00000523373.5 linkuse as main transcriptn.370G>A non_coding_transcript_exon_variant 4/115 ENSP00000430771.1 Q96DY7-3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460796
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726766
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

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 GeneticsSep 24, 2024The c.370G>A (p.V124I) alteration is located in exon 4 (coding exon 4) of the MTBP gene. This alteration results from a G to A substitution at nucleotide position 370, causing the valine (V) at amino acid position 124 to be replaced by an isoleucine (I). 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
Benign
0.080
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Benign
0.97
DEOGEN2
Benign
0.036
T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.025
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.00091
T
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.080
N
REVEL
Benign
0.023
Sift
Benign
0.32
T
Sift4G
Benign
0.48
T
Polyphen
0.0050
B
Vest4
0.14
MVP
0.36
MPC
0.13
ClinPred
0.14
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.055
gMVP
0.060

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377570872; hg19: chr8-121463507; API