Variant 8-120470887-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022045.5(MTBP):c.1115G>C(p.Ser372Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,612,344 control chromosomes in the GnomAD database, including 1 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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=0.19649291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTBP	NM_022045.5 linkuse as main transcript	c.1115G>C	p.Ser372Thr	missense_variant	11/22	ENST00000305949.6
MTBP	XM_011516962.3 linkuse as main transcript	c.1115G>C	p.Ser372Thr	missense_variant	11/18
MTBP	XM_011516963.3 linkuse as main transcript	c.1115G>C	p.Ser372Thr	missense_variant	11/14
MTBP	XR_928318.3 linkuse as main transcript	n.1167G>C		non_coding_transcript_exon_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.1115G>C	p.Ser372Thr	missense_variant	11/22	1	NM_022045.5	P1	Q96DY7-1
MTBP	ENST00000522449.1 linkuse as main transcript	n.312G>C		non_coding_transcript_exon_variant	4/4	1
MTBP	ENST00000523373.5 linkuse as main transcript	c.*130G>C		3_prime_UTR_variant, NMD_transcript_variant	11/11	5			Q96DY7-3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

250752

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135552

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

169

AN:

1460110

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

Jan 03, 2024

The c.1115G>C (p.S372T) alteration is located in exon 11 (coding exon 11) of the MTBP gene. This alteration results from a G to C substitution at nucleotide position 1115, causing the serine (S) at amino acid position 372 to be replaced by a threonine (T). 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

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.34

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

M_CAP

Benign

0.0092

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

0.90

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Uncertain

0.014

Sift4G

Uncertain

0.014

Polyphen

0.73

Vest4

0.45

MVP

0.42

MPC

0.50

ClinPred

0.25

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

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