Variant 8-120455498-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022045.5(MTBP):c.548A>G(p.Tyr183Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00356 in 1,606,810 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 94 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 100 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011426508).

BP6

Variant 8-120455498-A-G is Benign according to our data. Variant chr8-120455498-A-G is described in ClinVar as [Benign]. Clinvar id is 784137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTBP	NM_022045.5 linkuse as main transcript	c.548A>G	p.Tyr183Cys	missense_variant	6/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3 linkuse as main transcript	c.548A>G	p.Tyr183Cys	missense_variant	6/18		XP_011515264.1
MTBP	XM_011516963.3 linkuse as main transcript	c.548A>G	p.Tyr183Cys	missense_variant	6/14		XP_011515265.1
MTBP	XR_928318.3 linkuse as main transcript	n.600A>G		non_coding_transcript_exon_variant	6/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.548A>G	p.Tyr183Cys	missense_variant	6/22	1	NM_022045.5	ENSP00000303398	P1	Q96DY7-1
MTBP	ENST00000523373.5 linkuse as main transcript	c.548A>G	p.Tyr183Cys	missense_variant, NMD_transcript_variant	6/11	5		ENSP00000430771		Q96DY7-3

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2889

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00495

AC:

1238

AN:

250052

Hom.:

AF XY:

0.00342

AC XY:

463

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00194

AC:

2827

AN:

1454682

Hom.:

100

Cov.:

AF XY:

0.00164

AC XY:

1190

AN XY:

724154

show subpopulations

Gnomad4 AFR exome

AF:

0.0719

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.0190

AC:

2897

AN:

152128

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1361

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0666

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.0219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0729

AC:

321

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00624

AC:

757

Asia WGS

AF:

0.00376

AC:

AN:

3468

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.086

DEOGEN2

Benign

0.058

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

4.4

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.30

MVP

0.25

MPC

0.19

ClinPred

0.0076

GERP RS

5.6

Varity_R

0.073

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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