8-120445580-A-G

Position:

• chr8-120445580-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022045.5(MTBP):​c.110A>G​(p.Asn37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MTBP NM_022045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.314

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047742248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTBP	NM_022045.5	c.110A>G	p.Asn37Ser	missense_variant	1/22	ENST00000305949.6	NP_071328.2
MTBP	XM_011516962.3	c.110A>G	p.Asn37Ser	missense_variant	1/18		XP_011515264.1
MTBP	XM_011516963.3	c.110A>G	p.Asn37Ser	missense_variant	1/14		XP_011515265.1
MTBP	XR_928318.3	n.162A>G		non_coding_transcript_exon_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTBP	ENST00000305949.6	c.110A>G	p.Asn37Ser	missense_variant	1/22	1	NM_022045.5	ENSP00000303398	P1
MTBP	ENST00000456899.6	n.181A>G		non_coding_transcript_exon_variant	1/3	3
MTBP	ENST00000522308.1	n.159A>G		non_coding_transcript_exon_variant	1/4	2
MTBP	ENST00000523373.5	c.110A>G	p.Asn37Ser	missense_variant, NMD_transcript_variant	1/11	5		ENSP00000430771

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Sep 27, 2022

The c.110A>G (p.N37S) alteration is located in exon 1 (coding exon 1) of the MTBP gene. This alteration results from a A to G substitution at nucleotide position 110, causing the asparagine (N) at amino acid position 37 to be replaced by a serine (S). 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	0.075
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.69
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.015
Sift	Benign	0.22	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.15		Loss of catalytic residue at N37 (P = 0.0132);
MVP		0.24
MPC		0.12
ClinPred		0.056	T
GERP RS		2.6
Varity_R		0.026
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr8-121457820;