Variant chr8-120459231-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022045.5(MTBP):c.764G>A(p.Ser255Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MTBP
NM_022045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.422

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTBP	NM_022045.5 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	8/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	8/18		XP_011515264.1
MTBP	XM_011516963.3 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	8/14		XP_011515265.1
MTBP	XR_928318.3 linkuse as main transcript	n.816G>A		non_coding_transcript_exon_variant	8/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	8/22	1	NM_022045.5	ENSP00000303398	P1	Q96DY7-1
MTBP	ENST00000523373.5 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant, NMD_transcript_variant	8/11	5		ENSP00000430771		Q96DY7-3
MTBP	ENST00000522449.1 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248014

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

133984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456678

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Dec 01, 2022

The c.764G>A (p.S255N) alteration is located in exon 8 (coding exon 8) of the MTBP gene. This alteration results from a G to A substitution at nucleotide position 764, causing the serine (S) at amino acid position 255 to be replaced by an asparagine (N). 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

0.093

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.056

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.59

M_CAP

Benign

0.0026

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.97

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.52

REVEL

Benign

0.051

Sift

Benign

0.15

Sift4G

Benign

0.48

Polyphen

0.0040

Vest4

0.13

MutPred

0.32

Loss of sheet (P = 0.0817);

MVP

0.26

MPC

0.54

ClinPred

0.34

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: 23

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