Genetic Variant MIS18BP1:p.Lys887Arg (chr14-45223927-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018353.5(MIS18BP1):c.2660A>G(p.Lys887Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,570,824 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MIS18BP1
NM_018353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Publications

0 publications found

Variant links:

Genes affected

MIS18BP1 (HGNC:20190): (MIS18 binding protein 1) Predicted to enable DNA binding activity. Predicted to be involved in cell division. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIS18BP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16202638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018353.5. 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
	MIS18BP1	NM_018353.5	MANE Select	c.2660A>G	p.Lys887Arg	missense	Exon 11 of 17	NP_060823.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIS18BP1	ENST00000310806.9	TSL:1 MANE Select	c.2660A>G	p.Lys887Arg	missense	Exon 11 of 17	ENSP00000309790.4	Q6P0N0-1
MIS18BP1	ENST00000919501.1		c.2705A>G	p.Lys902Arg	missense	Exon 11 of 17	ENSP00000589560.1
MIS18BP1	ENST00000901126.1		c.2660A>G	p.Lys887Arg	missense	Exon 13 of 19	ENSP00000571185.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

216340

AF XY:

0.0000256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1418626

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

703954

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31238

American (AMR)

AF:

0.0000290

AC:

AN:

34490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23674

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

79446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49836

Middle Eastern (MID)

AF:

0.000905

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

1096620

Other (OTH)

AF:

0.0000513

AC:

AN:

58464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.62

M_CAP

Benign

0.0092

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.21

REVEL

Benign

0.048

Sift

Benign

0.55

Sift4G

Benign

0.35

Polyphen

0.35

Vest4

0.44

MutPred

0.41

Loss of methylation at K887 (P = 0.0204)

MVP

0.27

MPC

0.034

ClinPred

0.084

GERP RS

2.0

Varity_R

0.049

gMVP

0.10

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over