14-52663830-C-T

Variant names:

• chr14-52663830-C-T
• rs1172188263
• NM_014584.3:c.647G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014584.3(ERO1A):​c.647G>A​(p.Arg216Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,412,638 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. R216T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ERO1A NM_014584.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

Genes affected

ERO1A (HGNC:13280): (endoplasmic reticulum oxidoreductase 1 alpha) Enables oxidoreductase activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2208161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERO1A	NM_014584.3	c.647G>A	p.Arg216Lys	missense_variant	Exon 8 of 16	ENST00000395686.8	NP_055399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERO1A	ENST00000395686.8	c.647G>A	p.Arg216Lys	missense_variant	Exon 8 of 16	1	NM_014584.3	ENSP00000379042.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1412638 Hom.: 0 Cov.: 23 AF XY: 0.00000142 AC XY: 1 AN XY: 705290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000514

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.18
Sift	Benign	0.19	T;.
Sift4G	Benign	0.20	T;T
Polyphen		0.20	B;.
Vest4		0.39
MutPred		0.42		Gain of methylation at R216 (P = 0.0127);Gain of methylation at R216 (P = 0.0127);
MVP		0.26
MPC		1.0
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1172188263; hg19: chr14-53130548;