Genetic Variant MPHOSPH9:c.*501G>C (chr12-123156306-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022782.4(MPHOSPH9):c.*501G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,316 control chromosomes in the GnomAD database, including 53,283 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.83 ( 53252 hom., cov: 33)

Exomes 𝑓: 0.79 ( 31 hom. )

Consequence

MPHOSPH9
NM_022782.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.173

Publications

57 publications found

Variant links:

Genes affected

MPHOSPH9 (HGNC:7215): (M-phase phosphoprotein 9) Located in Golgi apparatus and centriole. Implicated in multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MPHOSPH9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH9	NM_022782.4 link	c.*501G>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000606320.6	NP_073619.3	Q99550

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MPHOSPH9	ENST00000606320.6 link	c.*501G>C	3_prime_UTR_variant	Exon 24 of 24	5	NM_022782.4	ENSP00000475489.1	Q99550
MPHOSPH9	ENST00000541603.6 link	c.553-3681G>C	intron_variant	Intron 5 of 5	1		ENSP00000446362.2	F5H1U6
MPHOSPH9	ENST00000541076.6 link	c.*501G>C	3_prime_UTR_variant	Exon 22 of 22	5		ENSP00000445859.2	A0A8I5IG87
MPHOSPH9	ENST00000545974.5 link	n.*93G>C	downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126840

AN:

152098

Hom.:

53197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.910

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.821

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.803

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.824

GnomAD4 exome

AF:

0.794

AC:

AN:

102

Hom.:

Cov.:

AF XY:

0.729

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.806

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.780

AC:

AN:

Other (OTH)

AF:

0.700

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.834

AC:

126947

AN:

152214

Hom.:

53252

Cov.:

AF XY:

0.833

AC XY:

61981

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.910

AC:

37824

AN:

41558

American (AMR)

AF:

0.821

AC:

12537

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.736

AC:

2554

AN:

3470

East Asian (EAS)

AF:

0.972

AC:

5045

AN:

5188

South Asian (SAS)

AF:

0.740

AC:

3572

AN:

4824

European-Finnish (FIN)

AF:

0.803

AC:

8494

AN:

10580

Middle Eastern (MID)

AF:

0.723

AC:

211

AN:

292

European-Non Finnish (NFE)

AF:

0.797

AC:

54209

AN:

68002

Other (OTH)

AF:

0.827

AC:

1746

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1077

2154

3230

4307

5384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.819

Hom.:

6363

Bravo

AF:

0.839

Asia WGS

AF:

0.871

AC:

3025

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.7

(source)

DANN

Benign

0.48

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over