Genetic Variant MEPCE:p.Pro18Leu (chr7-100430071-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019606.6(MEPCE):c.53C>T(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000359 in 1,113,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MEPCE
NM_019606.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Publications

1 publications found

Variant links:

Genes affected

MEPCE (HGNC:20247): (methylphosphate capping enzyme) Enables 7SK snRNA binding activity and RNA 5'-methyltransferase activity. Involved in RNA modification; positive regulation of protein localization to Cajal body; and positive regulation of snRNA transcription by RNA polymerase II. Located in nucleus. Part of 7SK snRNP. [provided by Alliance of Genome Resources, Apr 2022]

MEPCE links:

ENSG00000289690 (HGNC:):

ENSG00000289690 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14107814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019606.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEPCE	NM_019606.6	MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 1 of 4	NP_062552.2
MEPCE	NM_001194990.2		c.-811-544C>T		intron	N/A	NP_001181919.1	Q7L2J0-2
MEPCE	NM_001194991.2		c.-396-959C>T		intron	N/A	NP_001181920.1	Q7L2J0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEPCE	ENST00000310512.4	TSL:1 MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
ENSG00000289690	ENST00000695707.1		c.-396-959C>T		intron	N/A	ENSP00000512107.1
MEPCE	ENST00000715739.1		c.53C>T	p.Pro18Leu	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000359

AC:

AN:

1113708

Hom.:

Cov.:

AF XY:

0.00000377

AC XY:

AN XY:

530258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23146

American (AMR)

AF:

0.00

AC:

AN:

8540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14930

East Asian (EAS)

AF:

0.00

AC:

AN:

26632

South Asian (SAS)

AF:

0.00

AC:

AN:

29814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.00000320

AC:

AN:

937882

Other (OTH)

AF:

0.0000221

AC:

AN:

45192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000660

Hom.:

Bravo

AF:

0.00000378

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

0.15

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.016

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.98

REVEL

Benign

0.19

Sift

Uncertain

0.012

Sift4G

Benign

0.066

Polyphen

0.72

Vest4

0.32

MutPred

0.17

Loss of glycosylation at P18 (P = 0.0032)

MVP

0.14

MPC

2.1

ClinPred

0.90

GERP RS

4.4

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.21

gMVP

0.30

Mutation Taster

=79/21

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over