8-120446434-C-A

Variant summary

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

The NM_022045.5(MTBP):c.120C>A(p.Asp40Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MTBP
NM_022045.5 missense, splice_region

Scores

Splicing: ADA: 0.00006444

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.202

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]

MTBP links:

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=0.0910202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTBP	NM_022045.5 linkuse as main transcript	c.120C>A	p.Asp40Glu	missense_variant, splice_region_variant	2/22	ENST00000305949.6
MTBP	XM_011516962.3 linkuse as main transcript	c.120C>A	p.Asp40Glu	missense_variant, splice_region_variant	2/18
MTBP	XM_011516963.3 linkuse as main transcript	c.120C>A	p.Asp40Glu	missense_variant, splice_region_variant	2/14
MTBP	XR_928318.3 linkuse as main transcript	n.172C>A		splice_region_variant, non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.120C>A	p.Asp40Glu	missense_variant, splice_region_variant	2/22	1	NM_022045.5	P1	Q96DY7-1
MTBP	ENST00000456899.6 linkuse as main transcript	n.191C>A		splice_region_variant, non_coding_transcript_exon_variant	2/3	3
MTBP	ENST00000522308.1 linkuse as main transcript	n.169C>A		splice_region_variant, non_coding_transcript_exon_variant	2/4	2
MTBP	ENST00000523373.5 linkuse as main transcript	c.120C>A	p.Asp40Glu	missense_variant, splice_region_variant, NMD_transcript_variant	2/11	5			Q96DY7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250722

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1447808

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 28, 2023

The c.120C>A (p.D40E) alteration is located in exon 2 (coding exon 2) of the MTBP gene. This alteration results from a C to A substitution at nucleotide position 120, causing the aspartic acid (D) at amino acid position 40 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.89

DEOGEN2

Benign

0.025

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.52

M_CAP

Benign

0.0047

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.30

REVEL

Benign

0.041

Sift

Benign

0.18

Sift4G

Benign

0.83

Polyphen

0.83

Vest4

0.24

MutPred

0.21

Gain of helix (P = 0.0696);

MVP

0.41

MPC

0.57

ClinPred

0.26

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over