8-120517852-C-T

Variant names:

• chr8-120517852-C-T
• rs61753798
• NM_022045.5:c.2248C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022045.5(MTBP):​c.2248C>T​(p.Leu750Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,609,318 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (98 hom.)
• Consequence: MTBP NM_022045.5 missense, splice_region
• Scores: Splicing: ADA: 0.02131
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057896674).
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTBP	NM_022045.5	MANE Select	c.2248C>T	p.Leu750Phe	missense splice_region	Exon 19 of 22	NP_071328.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTBP	ENST00000305949.6	TSL:1 MANE Select	c.2248C>T	p.Leu750Phe	missense splice_region	Exon 19 of 22	ENSP00000303398.1	Q96DY7-1
	MTBP	ENST00000936432.1		c.2233C>T	p.Leu745Phe	missense splice_region	Exon 19 of 22	ENSP00000606491.1
	MTBP	ENST00000936431.1		c.2152C>T	p.Leu718Phe	missense splice_region	Exon 18 of 21	ENSP00000606490.1

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1035 AN: 151906 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00638

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00762 AC: 1898 AN: 249080 AF XY: 0.00829

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00554

Gnomad ASJ exome AF: 0.00271

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.00664

GnomAD4 exome AF: 0.00974 AC: 14200 AN: 1457294 Hom.: 98 Cov.: 36 AF XY: 0.00990 AC XY: 7179 AN XY: 725032

African (AFR) AF: 0.00171 AC: 57 AN: 33366

American (AMR) AF: 0.00571 AC: 254 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00315 AC: 82 AN: 26004

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39634

South Asian (SAS) AF: 0.0132 AC: 1136 AN: 85942

European-Finnish (FIN) AF: 0.00252 AC: 134 AN: 53202

Middle Eastern (MID) AF: 0.00924 AC: 53 AN: 5736

European-Non Finnish (NFE) AF: 0.0108 AC: 11992 AN: 1108760

Other (OTH) AF: 0.00815 AC: 490 AN: 60152

GnomAD4 genome AF: 0.00680 AC: 1034 AN: 152024 Hom.: 8 Cov.: 32 AF XY: 0.00678 AC XY: 504 AN XY: 74322

African (AFR) AF: 0.00188 AC: 78 AN: 41520

American (AMR) AF: 0.00637 AC: 97 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 11 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4818

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10598

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 746 AN: 67906

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00904 Hom.: 23

Bravo AF: 0.00672

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0113 AC: 97

ExAC AF: 0.00799 AC: 970

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.0113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.68
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.036
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.36	B
Vest4		0.14
MVP		0.64
MPC		0.20
ClinPred		0.015	T
GERP RS		2.7
Varity_R		0.086
gMVP		0.25
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs61753798; hg19: chr8-121530092;