chr8-120456573-A-T

Position:

• chr8-120456573-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022045.5(MTBP):​c.650A>T​(p.Glu217Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTBP NM_022045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36550862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTBP	NM_022045.5	c.650A>T	p.Glu217Val	missense_variant	7/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3	c.650A>T	p.Glu217Val	missense_variant	7/18		XP_011515264.1
MTBP	XM_011516963.3	c.650A>T	p.Glu217Val	missense_variant	7/14		XP_011515265.1
MTBP	XR_928318.3	n.702A>T		non_coding_transcript_exon_variant	7/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6	c.650A>T	p.Glu217Val	missense_variant	7/22	1	NM_022045.5	ENSP00000303398	P1
MTBP	ENST00000523373.5	c.650A>T	p.Glu217Val	missense_variant, NMD_transcript_variant	7/11	5		ENSP00000430771

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.650A>T (p.E217V) alteration is located in exon 7 (coding exon 7) of the MTBP gene. This alteration results from a A to T substitution at nucleotide position 650, causing the glutamic acid (E) at amino acid position 217 to be replaced by a valine (V). 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	0.25
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.87	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.064	T
Sift4G	Benign	0.15	T
Polyphen		0.62	P
Vest4		0.51
MutPred		0.37		Gain of catalytic residue at S220 (P = 0.0445);
MVP		0.53
MPC		0.68
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.14
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-121468813;