10-32271753-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001272004.3(EPC1):c.2170A>T(p.Thr724Ser) 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. 14/20 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)
• Consequence: EPC1 NM_001272004.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, EPC1
• BP4: Computational evidence support a benign effect (MetaRNN=0.36246014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPC1	NM_001272004.3	c.2170A>T	p.Thr724Ser	missense_variant	13/14	ENST00000319778.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPC1	ENST00000319778.11	c.2170A>T	p.Thr724Ser	missense_variant	13/14	1	NM_001272004.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.2239A>T (p.T747S) alteration is located in exon 14 (coding exon 14) of the EPC1 gene. This alteration results from a A to T substitution at nucleotide position 2239, causing the threonine (T) at amino acid position 747 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	17
Dann	Benign	0.96
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.28	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.093	B;B;B
Vest4		0.56
MutPred		0.66		.;.;Gain of disorder (P = 0.0627);
MVP		0.18
MPC		0.79
ClinPred		0.26	T
GERP RS		4.2
Varity_R		0.027
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-32560681;