7-100430347-C-G

Variant names:

• chr7-100430347-C-G
• rs1798606967
• NM_019606.6:c.329C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019606.6(MEPCE):​c.329C>G​(p.Pro110Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000783 in 1,277,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.8e-7 (0 hom.)
• Consequence: MEPCE NM_019606.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.396
• Publications: 0 publications found

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]

ENSG00000289690 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06490761).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPCE	NM_019606.6	MANE Select	c.329C>G	p.Pro110Arg	missense	Exon 1 of 4	NP_062552.2
	MEPCE	NM_001194990.2		c.-811-268C>G		intron	N/A	NP_001181919.1	Q7L2J0-2
	MEPCE	NM_001194991.2		c.-396-683C>G		intron	N/A	NP_001181920.1	Q7L2J0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPCE	ENST00000310512.4	TSL:1 MANE Select	c.329C>G	p.Pro110Arg	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
	ENSG00000289690	ENST00000695707.1		c.-396-683C>G		intron	N/A	ENSP00000512107.1
	MEPCE	ENST00000715739.1		c.329C>G	p.Pro110Arg	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.83e-7 AC: 1 AN: 1277686 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 618740

African (AFR) AF: 0.00 AC: 0 AN: 28094

American (AMR) AF: 0.00 AC: 0 AN: 19220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18680

East Asian (EAS) AF: 0.00 AC: 0 AN: 34154

South Asian (SAS) AF: 0.00 AC: 0 AN: 62928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3982

European-Non Finnish (NFE) AF: 9.74e-7 AC: 1 AN: 1026794

Other (OTH) AF: 0.00 AC: 0 AN: 53036

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.40
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.0	N
REVEL	Benign	0.026
Sift	Uncertain	0.014	D
Sift4G	Benign	0.22	T
Polyphen		0.28	B
Vest4		0.21
MutPred		0.29		Gain of MoRF binding (P = 0.0073)
MVP		0.082
MPC		1.4
ClinPred		0.25	T
GERP RS		-0.20
Varity_R		0.059
gMVP		0.15
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1798606967; hg19: chr7-100027970;