10-32346906-G-T

Variant names:

• chr10-32346906-G-T
• rs11597888
• NM_001272004.3:c.10C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001272004.3(EPC1):​c.10C>A​(p.Leu4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPC1 NM_001272004.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 18 publications found

Genes affected

EPC1 (HGNC:19876): (enhancer of polycomb homolog 1) This gene encodes a member of the polycomb group (PcG) family. The encoded protein is a component of the NuA4 histone acetyltransferase complex and can act as both a transcriptional activator and repressor. The encoded protein has been linked to apoptosis, DNA repair, skeletal muscle differentiation, gene silencing, and adult T-cell leukemia/lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

EPC1-AS2 (HGNC:56646): (EPC1 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32770273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272004.3. 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
	EPC1	NM_001272004.3	MANE Select	c.10C>A	p.Leu4Met	missense	Exon 1 of 14	NP_001258933.1
	EPC1	NM_025209.5		c.10C>A	p.Leu4Met	missense	Exon 1 of 15	NP_079485.1
	EPC1	NM_001382753.1		c.10C>A	p.Leu4Met	missense	Exon 1 of 14	NP_001369682.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPC1	ENST00000319778.11	TSL:1 MANE Select	c.10C>A	p.Leu4Met	missense	Exon 1 of 14	ENSP00000318559.6
	EPC1	ENST00000263062.8	TSL:1	c.10C>A	p.Leu4Met	missense	Exon 1 of 15	ENSP00000263062.8
	EPC1	ENST00000375110.6	TSL:1	c.3+31585C>A		intron	N/A	ENSP00000364251.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.22		Gain of MoRF binding (P = 0.0739)
MVP		0.45
MPC		2.4
ClinPred		0.98	D
GERP RS		3.7
PromoterAI		0.16	Neutral
Varity_R		0.79
gMVP		0.70
Mutation Taster		=71/29	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: rs11597888; hg19: chr10-32635834;