chr12-112022224-C-T

Variant names:

• chr12-112022224-C-T
• rs146674309
• NM_006817.4:c.358C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006817.4(ERP29):​c.358C>T​(p.Leu120Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: ERP29 NM_006817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 3 publications found

Genes affected

ERP29 (HGNC:13799): (endoplasmic reticulum protein 29) This gene encodes a protein which localizes to the lumen of the endoplasmic reticulum (ER). It is a member of the protein disulfide isomerase (PDI) protein family but lacks an active thioredoxin motif, suggesting that this protein does not function as a disulfide isomerase. The canonical protein dimerizes and is thought to play a role in the processing of secretory proteins within the ER. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

LOC124903021 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21510881).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006817.4. 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
	ERP29	NM_006817.4	MANE Select	c.358C>T	p.Leu120Phe	missense	Exon 3 of 3	NP_006808.1	P30040-1
	ERP29	NM_001034025.2		c.*57C>T		3_prime_UTR	Exon 2 of 2	NP_001029197.1	P30040-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERP29	ENST00000261735.4	TSL:1 MANE Select	c.358C>T	p.Leu120Phe	missense	Exon 3 of 3	ENSP00000261735.3	P30040-1
	ERP29	ENST00000880255.1		c.358C>T	p.Leu120Phe	missense	Exon 4 of 4	ENSP00000550314.1
	ERP29	ENST00000880256.1		c.358C>T	p.Leu120Phe	missense	Exon 4 of 4	ENSP00000550315.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152238 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251230 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461752 Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19 AN XY: 727204

African (AFR) AF: 0.00128 AC: 43 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111926

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152356 Hom.: 1 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74502

African (AFR) AF: 0.000577 AC: 24 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000257

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.60
MVP		0.38
MPC		0.71
ClinPred		0.45	T
GERP RS		5.3
Varity_R		0.87
gMVP		0.54
Mutation Taster		=49/51	disease causing

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: rs146674309; hg19: chr12-112460028; COSMIC: COSV55673487; COSMIC: COSV55673487;