Variant 8-120456659-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022045.5(MTBP):c.736T>C(p.Trp246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,558,812 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0117916465).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTBP	NM_022045.5 linkuse as main transcript	c.736T>C	p.Trp246Arg	missense_variant	7/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3 linkuse as main transcript	c.736T>C	p.Trp246Arg	missense_variant	7/18		XP_011515264.1
MTBP	XM_011516963.3 linkuse as main transcript	c.736T>C	p.Trp246Arg	missense_variant	7/14		XP_011515265.1
MTBP	XR_928318.3 linkuse as main transcript	n.788T>C		non_coding_transcript_exon_variant	7/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.736T>C	p.Trp246Arg	missense_variant	7/22	1	NM_022045.5	ENSP00000303398	P1	Q96DY7-1
MTBP	ENST00000523373.5 linkuse as main transcript	c.736T>C	p.Trp246Arg	missense_variant, NMD_transcript_variant	7/11	5		ENSP00000430771		Q96DY7-3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000445

AC:

105

AN:

236104

Hom.:

AF XY:

0.000454

AC XY:

AN XY:

127802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00798

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.000522

GnomAD4 exome

AF:

0.000230

AC:

324

AN:

1406718

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

162

AN XY:

702252

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000240

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000739

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000217

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000338

AC:

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

Oct 18, 2021

The c.736T>C (p.W246R) alteration is located in exon 7 (coding exon 7) of the MTBP gene. This alteration results from a T to C substitution at nucleotide position 736, causing the tryptophan (W) at amino acid position 246 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.39

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.55

M_CAP

Benign

0.0050

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.59

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.14

Sift

Benign

0.90

Sift4G

Benign

0.85

Polyphen

0.17

Vest4

0.43

MutPred

0.51

Gain of ubiquitination at K249 (P = 0.086);

MVP

0.33

MPC

0.87

ClinPred

0.065

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.41

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.

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