Genetic Variant NM_019606.6:c.269C>A (chr7-100430287-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.269C>A(p.Pro90His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 1,253,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000024 ( 0 hom. )

Consequence

MEPCE
NM_019606.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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=0.14096564).

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.269C>A	p.Pro90His	missense	Exon 1 of 4	NP_062552.2
MEPCE	NM_001194990.2		c.-811-328C>A		intron	N/A	NP_001181919.1	Q7L2J0-2
MEPCE	NM_001194991.2		c.-396-743C>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.269C>A	p.Pro90His	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
ENSG00000289690	ENST00000695707.1		c.-396-743C>A		intron	N/A	ENSP00000512107.1
MEPCE	ENST00000715739.1		c.269C>A	p.Pro90His	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000239

AC:

AN:

1253766

Hom.:

Cov.:

AF XY:

0.00000330

AC XY:

AN XY:

605250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26836

American (AMR)

AF:

0.00

AC:

AN:

17028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18068

East Asian (EAS)

AF:

0.00

AC:

AN:

32312

South Asian (SAS)

AF:

0.00

AC:

AN:

57964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3588

European-Non Finnish (NFE)

AF:

0.00000295

AC:

AN:

1016156

Other (OTH)

AF:

0.00

AC:

AN:

51984

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

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

0.085

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.058

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.46

M_CAP

Benign

0.035

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.14

REVEL

Benign

0.044

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.032

Polyphen

0.79

Vest4

0.26

MutPred

0.27

Gain of MoRF binding (P = 0.0526)

MVP

0.13

MPC

1.9

ClinPred

0.74

GERP RS

3.4

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.24

gMVP

0.40

Mutation Taster

=77/23

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

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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