7-100430064-C-T

Variant names:

• chr7-100430064-C-T
• rs992838688
• NM_019606.6:c.46C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019606.6(MEPCE):​c.46C>T​(p.Pro16Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000899 in 1,112,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P16A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: MEPCE NM_019606.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• 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: 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=0.13559526).

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.46C>T	p.Pro16Ser	missense	Exon 1 of 4	NP_062552.2
	MEPCE	NM_001194990.2		c.-811-551C>T		intron	N/A	NP_001181919.1	Q7L2J0-2
	MEPCE	NM_001194991.2		c.-396-966C>T		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.46C>T	p.Pro16Ser	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
	ENSG00000289690	ENST00000695707.1		c.-396-966C>T		intron	N/A	ENSP00000512107.1
	MEPCE	ENST00000715739.1		c.46C>T	p.Pro16Ser	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.99e-7 AC: 1 AN: 1112272 Hom.: 0 Cov.: 30 AF XY: 0.00000189 AC XY: 1 AN XY: 529382

African (AFR) AF: 0.0000432 AC: 1 AN: 23122

American (AMR) AF: 0.00 AC: 0 AN: 8538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14930

East Asian (EAS) AF: 0.00 AC: 0 AN: 26628

South Asian (SAS) AF: 0.00 AC: 0 AN: 29466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 937012

Other (OTH) AF: 0.00 AC: 0 AN: 45134

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.063
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.078	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.20		Gain of phosphorylation at P16 (P = 0.0106)
MVP		0.26
MPC		2.1
ClinPred		0.72	D
GERP RS		4.1
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.32
gMVP		0.25
Mutation Taster		=79/21	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: rs992838688; hg19: chr7-100027687;