Variant 13-19650245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000361479.10(MPHOSPH8):c.1561G>A(p.Ala521Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MPHOSPH8
ENST00000361479.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0660

Variant links:

Genes affected

MPHOSPH8 (HGNC:29810): (M-phase phosphoprotein 8) Enables chromatin binding activity and methylated histone binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; regulation of DNA methylation; and regulation of gene expression. Located in several cellular components, including cytosol; heterochromatin; and nuclear lumen. Part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]

MPHOSPH8 links:

MPHOSPH8 (HGNC:):

MPHOSPH8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026833892).

BP6

Variant 13-19650245-G-A is Benign according to our data. Variant chr13-19650245-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3295682.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPHOSPH8	NM_017520.4 linkuse as main transcript	c.1561G>A	p.Ala521Thr	missense_variant	5/14	ENST00000361479.10	NP_059990.2	Q99549-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPHOSPH8	ENST00000361479.10 linkuse as main transcript	c.1561G>A	p.Ala521Thr	missense_variant	5/14	1	NM_017520.4	ENSP00000355388.4		Q99549-1
MPHOSPH8	ENST00000414242.3 linkuse as main transcript	c.880G>A	p.Ala294Thr	missense_variant	3/3	1		ENSP00000414663.3		A0A0A0MT47

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250440

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000110

AC:

160

AN:

1460936

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.18

DANN

Benign

0.16

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.68

M_CAP

Benign

0.0051

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.75

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

0.61

Polyphen

0.0010

Vest4

0.018

MVP

0.26

MPC

0.23

ClinPred

0.0060

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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