8-120490555-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022045.5(MTBP):c.1432T>G(p.Leu478Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,599,320 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (22 hom.)
• Consequence: MTBP NM_022045.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006462723).
• BP6: Variant 8-120490555-T-G is Benign according to our data. Variant chr8-120490555-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTBP	NM_022045.5	c.1432T>G	p.Leu478Val	missense_variant	13/22	ENST00000305949.6
MTBP	XM_011516962.3	c.1432T>G	p.Leu478Val	missense_variant	13/18
MTBP	XM_011516963.3	c.1432T>G	p.Leu478Val	missense_variant	13/14
MTBP	XR_928318.3	n.1484T>G		non_coding_transcript_exon_variant	13/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTBP	ENST00000305949.6	c.1432T>G	p.Leu478Val	missense_variant	13/22	1	NM_022045.5	P1
MTBP	ENST00000519188.1	n.265T>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152172 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00238 AC: 574 AN: 240686 Hom.: 6 AF XY: 0.00253 AC XY: 329 AN XY: 129958

Gnomad AFR exome AF: 0.000314

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00425

Gnomad EAS exome AF: 0.0000568

Gnomad SAS exome AF: 0.00828

Gnomad FIN exome AF: 0.00168

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.00209 AC: 3020 AN: 1447030 Hom.: 22 Cov.: 28 AF XY: 0.00225 AC XY: 1617 AN XY: 719730

Gnomad4 AFR exome AF: 0.000183

Gnomad4 AMR exome AF: 0.000639

Gnomad4 ASJ exome AF: 0.00466

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00815

Gnomad4 FIN exome AF: 0.00233

Gnomad4 NFE exome AF: 0.00175

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00142 AC: 217 AN: 152290 Hom.: 3 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74466

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00170 Hom.: 1

Bravo AF: 0.00108

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00260 AC: 316

Asia WGS AF: 0.00809 AC: 28 AN: 3474

EpiCase AF: 0.00142

EpiControl AF: 0.00125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MTBP: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.019
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.054	B
Vest4		0.24
MVP		0.25
MPC		0.17
ClinPred		0.0065	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.48

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

Other links and lift over

dbSNP: rs148151530; hg19: chr8-121502795;