dbSNP rs1051431: MPHOSPH9:p.Tyr1087Tyr (chr12-123161256-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022782.4(MPHOSPH9):c.3261C>T(p.Tyr1087Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,613,812 control chromosomes in the GnomAD database, including 473,646 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 0.64 ( 35267 hom., cov: 31)

Exomes 𝑓: 0.77 ( 438379 hom. )

Consequence

MPHOSPH9
NM_022782.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.399

Publications

43 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.399 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022782.4. 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
	MPHOSPH9	NM_022782.4	MANE Select	c.3261C>T	p.Tyr1087Tyr	synonymous	Exon 22 of 24	NP_073619.3
	MPHOSPH9	NR_103517.2		n.3225C>T		non_coding_transcript_exon	Exon 22 of 24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPHOSPH9	ENST00000606320.6	TSL:5 MANE Select	c.3261C>T	p.Tyr1087Tyr	synonymous	Exon 22 of 24	ENSP00000475489.1	Q99550-1
MPHOSPH9	ENST00000541603.6	TSL:1	c.363C>T	p.Tyr121Tyr	synonymous	Exon 4 of 6	ENSP00000446362.2	F5H1U6
MPHOSPH9	ENST00000302373.8	TSL:1	n.*112C>T		non_coding_transcript_exon	Exon 16 of 18	ENSP00000304096.5	J3KNE4

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96580

AN:

151944

Hom.:

35257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.737

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.673

GnomAD2 exomes

AF:

0.742

AC:

186445

AN:

251428

AF XY:

0.749

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.725

Gnomad ASJ exome

AF:

0.688

Gnomad EAS exome

AF:

0.974

Gnomad FIN exome

AF:

0.807

Gnomad NFE exome

AF:

0.777

Gnomad OTH exome

AF:

0.760

GnomAD4 exome

AF:

0.769

AC:

1123368

AN:

1461750

Hom.:

438379

Cov.:

AF XY:

0.768

AC XY:

558210

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.228

AC:

7620

AN:

33480

American (AMR)

AF:

0.725

AC:

32426

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

17996

AN:

26134

East Asian (EAS)

AF:

0.975

AC:

38678

AN:

39690

South Asian (SAS)

AF:

0.725

AC:

62550

AN:

86252

European-Finnish (FIN)

AF:

0.807

AC:

43130

AN:

53416

Middle Eastern (MID)

AF:

0.653

AC:

3767

AN:

5768

European-Non Finnish (NFE)

AF:

0.784

AC:

871869

AN:

1111894

Other (OTH)

AF:

0.751

AC:

45332

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15038

30075

45113

60150

75188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20500

41000

61500

82000

102500

<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:

0.635

AC:

96615

AN:

152062

Hom.:

35267

Cov.:

AF XY:

0.642

AC XY:

47742

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.251

AC:

10397

AN:

41410

American (AMR)

AF:

0.736

AC:

11246

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2323

AN:

3472

East Asian (EAS)

AF:

0.972

AC:

5034

AN:

5180

South Asian (SAS)

AF:

0.732

AC:

3529

AN:

4824

European-Finnish (FIN)

AF:

0.802

AC:

8491

AN:

10592

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.783

AC:

53238

AN:

67992

Other (OTH)

AF:

0.676

AC:

1425

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1350

2700

4049

5399

6749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.724

Hom.:

66033

Bravo

AF:

0.611

Asia WGS

AF:

0.821

AC:

2852

AN:

3478

EpiCase

AF:

0.765

EpiControl

AF:

0.770

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

(source)

DANN

Benign

0.45

PhyloP100

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over