NM_152321.4:c.789A>C

Variant names:

• chr12-14914768-T-G
• NM_152321.4:c.789A>C

Variant summary

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

The NM_152321.4(ERP27):​c.789A>C​(p.Glu263Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERP27 NM_152321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.148
• Publications: 0 publications found

Genes affected

ERP27 (HGNC:26495): (endoplasmic reticulum protein 27) This gene encodes a noncatalytic member of the protein disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins. The canonical protein has an N-terminal signal sequence, two thioredoxin (TRX)-like domains and a C-terminal ER-retention sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms; some of which lack domains present in the canonical protein. [provided by RefSeq, Dec 2016]

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=0.06875399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERP27	NM_152321.4	c.789A>C	p.Glu263Asp	missense_variant	Exon 7 of 7	ENST00000266397.7	NP_689534.1
ERP27	NM_001300784.2	c.486A>C	p.Glu162Asp	missense_variant	Exon 5 of 5		NP_001287713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERP27	ENST00000266397.7	c.789A>C	p.Glu263Asp	missense_variant	Exon 7 of 7	1	NM_152321.4	ENSP00000266397.2
ERP27	ENST00000540097.1	c.486A>C	p.Glu162Asp	missense_variant	Exon 5 of 5	2		ENSP00000440573.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.789A>C (p.E263D) alteration is located in exon 7 (coding exon 7) of the ERP27 gene. This alteration results from a A to C substitution at nucleotide position 789, causing the glutamic acid (E) at amino acid position 263 to be replaced by an aspartic acid (D). 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	0.087
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.9
DANN	Benign	0.77
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PhyloP100		-0.15
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.013
Sift	Benign	0.18	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0030	B;.
Vest4		0.060
MutPred		0.21		Loss of stability (P = 0.2267);.;
MVP		0.43
MPC		0.038
ClinPred		0.041	T
GERP RS		2.1
Varity_R		0.069
gMVP		0.41
Mutation Taster		=89/11	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

hg19: chr12-15067702;