Genetic Variant NM_018353.5:c.3259A>G (chr14-45204435-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018353.5(MIS18BP1):c.3259A>G(p.Thr1087Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000964 in 1,452,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MIS18BP1
NM_018353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05654916).

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.3259A>G	p.Thr1087Ala	missense	Exon 16 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.3259A>G	p.Thr1087Ala	missense	Exon 16 of 17	ENSP00000309790.4	Q6P0N0-1
MIS18BP1	ENST00000919501.1		c.3304A>G	p.Thr1102Ala	missense	Exon 16 of 17	ENSP00000589560.1
MIS18BP1	ENST00000901126.1		c.3259A>G	p.Thr1087Ala	missense	Exon 18 of 19	ENSP00000571185.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000249

AC:

AN:

240898

AF XY:

0.00000766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000964

AC:

AN:

1452120

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32822

American (AMR)

AF:

0.000191

AC:

AN:

41914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25888

East Asian (EAS)

AF:

0.00

AC:

AN:

39302

South Asian (SAS)

AF:

0.00

AC:

AN:

84470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108732

Other (OTH)

AF:

0.0000667

AC:

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000600

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

0.096

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.45

M_CAP

Benign

0.0081

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

-0.017

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.0

REVEL

Benign

0.041

Sift

Benign

0.10

Sift4G

Benign

0.090

Polyphen

0.0020

Vest4

0.16

MutPred

0.22

Gain of catalytic residue at R1091 (P = 0.0032)

MVP

0.040

MPC

0.024

ClinPred

0.048

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.034

gMVP

0.30

Mutation Taster

=88/12

polymorphism

(source)

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

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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