Genetic Variant MPHOSPH8:p.Ser85Leu (chr13-19642155-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017520.4(MPHOSPH8):c.254C>T(p.Ser85Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,454,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MPHOSPH8
NM_017520.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

Publications

0 publications found

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:

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new If you want to explore the variant's impact on the transcript NM_017520.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017520.4. 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
	MPHOSPH8	NM_017520.4	MANE Select	c.254C>T	p.Ser85Leu	missense	Exon 2 of 14	NP_059990.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPHOSPH8	ENST00000361479.10	TSL:1 MANE Select	c.254C>T	p.Ser85Leu	missense	Exon 2 of 14	ENSP00000355388.4	Q99549-1
MPHOSPH8	ENST00000971230.1		c.254C>T	p.Ser85Leu	missense	Exon 2 of 15	ENSP00000641289.1
MPHOSPH8	ENST00000971229.1		c.254C>T	p.Ser85Leu	missense	Exon 2 of 14	ENSP00000641288.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000808

AC:

AN:

247382

AF XY:

0.00000747

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454278

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723448

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33058

American (AMR)

AF:

0.00

AC:

AN:

43762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39190

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108192

Other (OTH)

AF:

0.00

AC:

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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.:

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

0.18

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.42

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.7

PhyloP100

7.2

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.49

Mutation Taster

=19/81

disease causing

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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