Genetic Variant MIS18BP1:p.Thr1087Ala (chr14-45204435-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_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. 14/21 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

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity M18BP_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIS18BP1	NM_018353.5 link	c.3259A>G	p.Thr1087Ala	missense_variant	Exon 16 of 17	ENST00000310806.9	NP_060823.3	Q6P0N0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIS18BP1	ENST00000310806.9 link	c.3259A>G	p.Thr1087Ala	missense_variant	Exon 16 of 17	1	NM_018353.5	ENSP00000309790.4	Q6P0N0-1
MIS18BP1	ENST00000470424.1 link	n.381A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
MIS18BP1	ENST00000496413.1 link	n.211A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000249

AC:

AN:

240898

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130632

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000191

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000600

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3259A>G (p.T1087A) alteration is located in exon 16 (coding exon 15) of the MIS18BP1 gene. This alteration results from a A to G substitution at nucleotide position 3259, causing the threonine (T) at amino acid position 1087 to be replaced by an alanine (A). 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

0.096

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.61

CADD

Benign

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over