Genetic Variant MPHOSPH10:c.-291C>T (chr2-71130375-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000498451(MPHOSPH10):c.-291C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 851,090 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 374 hom., cov: 34)

Exomes 𝑓: 0.0080 ( 215 hom. )

Consequence

MPHOSPH10
ENST00000498451 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.621

Variant links:

Genes affected

MPHOSPH10 (HGNC:7213): (M-phase phosphoprotein 10) This gene encodes a protein that is phosphorylated during mitosis. The protein localizes to the nucleolus during interphase and to the chromosomes during M phase. The protein associates with the U3 small nucleolar ribonucleoprotein 60-80S complexes and may be involved in pre-rRNA processing. [provided by RefSeq, Dec 2010]

MPHOSPH10 links:

MCEE (HGNC:16732): (methylmalonyl-CoA epimerase) The product of this gene catalyzes the interconversion of D- and L-methylmalonyl-CoA during the degradation of branched chain amino acids. odd chain-length fatty acids, and other metabolites. Mutations in this gene result in methylmalonyl-CoA epimerase deficiency, which is presented as mild to moderate methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MCEE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-71130375-C-T is Benign according to our data. Variant chr2-71130375-C-T is described in ClinVar as [Benign]. Clinvar id is 1237378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MCEE	NM_032601.4 link	c.-156G>A	upstream_gene_variant	ENST00000244217.6	NP_115990.3	Q96PE7
MCEE	XM_047446039.1 link	c.-156G>A	upstream_gene_variant		XP_047301995.1
MCEE	XM_005264613.3 link	c.-156G>A	upstream_gene_variant		XP_005264670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCEE	ENST00000244217.6 link	c.-156G>A		upstream_gene_variant		1	NM_032601.4	ENSP00000244217.5		Q96PE7

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6192

AN:

152192

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00961

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.00800

AC:

5589

AN:

698780

Hom.:

215

Cov.:

AF XY:

0.00744

AC XY:

2737

AN XY:

367962

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.00899

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00544

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.000106

Gnomad4 NFE exome

AF:

0.00269

Gnomad4 OTH exome

AF:

0.0164

GnomAD4 genome

AF:

0.0407

AC:

6193

AN:

152310

Hom.:

374

Cov.:

AF XY:

0.0388

AC XY:

2891

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00963

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.7

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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