dbSNP rs1366809772: MEPCE:p.Pro10Gln (chr7-100430047-C-A) – 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.29C>A(p.Pro10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000895 in 1,117,654 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

MEPCE
NM_019606.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.30

Publications

0 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=0.23133007).

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.29C>A	p.Pro10Gln	missense	Exon 1 of 4	NP_062552.2
MEPCE	NM_001194990.2		c.-811-568C>A		intron	N/A	NP_001181919.1	Q7L2J0-2
MEPCE	NM_001194991.2		c.-396-983C>A		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.29C>A	p.Pro10Gln	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
ENSG00000289690	ENST00000695707.1		c.-396-983C>A		intron	N/A	ENSP00000512107.1
MEPCE	ENST00000715739.1		c.29C>A	p.Pro10Gln	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.95e-7

AC:

AN:

1117654

Hom.:

Cov.:

AF XY:

0.00000188

AC XY:

AN XY:

532316

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23192

American (AMR)

AF:

0.00

AC:

AN:

8552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15010

East Asian (EAS)

AF:

0.00

AC:

AN:

26668

South Asian (SAS)

AF:

0.00

AC:

AN:

30548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4386

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

940454

Other (OTH)

AF:

0.00

AC:

AN:

45416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

M_CAP

Benign

0.054

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

PhyloP100

3.3

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.70

REVEL

Benign

0.089

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.93

Vest4

0.44

MutPred

0.15

Gain of helix (P = 0.0325)

MVP

0.22

MPC

1.7

ClinPred

0.72

GERP RS

5.2

PromoterAI

-0.0014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.43

gMVP

0.26

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over