Variant 8-120453852-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_StrongBS1BS2

The NM_022045.5(MTBP):c.431A>G(p.Tyr144Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,572,622 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 30 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.20

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=0.010437548).

BP6

Variant 8-120453852-A-G is Benign according to our data. Variant chr8-120453852-A-G is described in ClinVar as [Benign]. Clinvar id is 774248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1213/152202) while in subpopulation AFR AF= 0.0216 (898/41558). AF 95% confidence interval is 0.0204. There are 14 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTBP	NM_022045.5 linkuse as main transcript	c.431A>G	p.Tyr144Cys	missense_variant	5/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3 linkuse as main transcript	c.431A>G	p.Tyr144Cys	missense_variant	5/18		XP_011515264.1
MTBP	XM_011516963.3 linkuse as main transcript	c.431A>G	p.Tyr144Cys	missense_variant	5/14		XP_011515265.1
MTBP	XR_928318.3 linkuse as main transcript	n.483A>G		non_coding_transcript_exon_variant	5/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.431A>G	p.Tyr144Cys	missense_variant	5/22	1	NM_022045.5	ENSP00000303398	P1	Q96DY7-1
MTBP	ENST00000523373.5 linkuse as main transcript	c.431A>G	p.Tyr144Cys	missense_variant, NMD_transcript_variant	5/11	5		ENSP00000430771		Q96DY7-3

Frequencies

GnomAD3 genomes

AF:

0.00795

AC:

1209

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00395

AC:

951

AN:

240620

Hom.:

AF XY:

0.00374

AC XY:

487

AN XY:

130300

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.00577

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.0000579

Gnomad SAS exome

AF:

0.00305

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00232

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00248

AC:

3523

AN:

1420420

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1805

AN XY:

707600

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.00603

Gnomad4 ASJ exome

AF:

0.00513

Gnomad4 EAS exome

AF:

0.0000781

Gnomad4 SAS exome

AF:

0.00396

Gnomad4 FIN exome

AF:

0.0000949

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00797

AC:

1213

AN:

152202

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

583

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00944

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00425

AC:

516

Asia WGS

AF:

0.00319

AC:

AN:

3464

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	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.79

MVP

0.51

MPC

0.33

ClinPred

0.038

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.42

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