chr3-142818389-C-T

Variant names:

• chr3-142818389-C-T
• rs373839458
• NM_013363.4:c.1194G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013363.4(PCOLCE2):​c.1194G>A​(p.Met398Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PCOLCE2 NM_013363.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.420
• Publications: 0 publications found

Genes affected

PCOLCE2 (HGNC:8739): (procollagen C-endopeptidase enhancer 2) Enables collagen binding activity; heparin binding activity; and peptidase activator activity. Predicted to be involved in positive regulation of peptidase activity. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066988885).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013363.4. 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
	PCOLCE2	NM_013363.4	MANE Select	c.1194G>A	p.Met398Ile	missense	Exon 9 of 9	NP_037495.1	Q9UKZ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCOLCE2	ENST00000295992.8	TSL:1 MANE Select	c.1194G>A	p.Met398Ile	missense	Exon 9 of 9	ENSP00000295992.3	Q9UKZ9
	PCOLCE2	ENST00000964680.1		c.1251G>A	p.Met417Ile	missense	Exon 10 of 10	ENSP00000634739.1
	PCOLCE2	ENST00000964678.1		c.1188G>A	p.Met396Ile	missense	Exon 9 of 9	ENSP00000634737.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249404 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461210 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726958

African (AFR) AF: 0.000149 AC: 5 AN: 33464

American (AMR) AF: 0.000134 AC: 6 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152020 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74256

African (AFR) AF: 0.000145 AC: 6 AN: 41382

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

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	Benign	0.29
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.0073
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.42
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.084
Sift	Benign	0.11	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.64		Loss of sheet (P = 0.0181)
MVP		0.19
MPC		0.16
ClinPred		0.066	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.31
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

dbSNP: rs373839458; hg19: chr3-142537231;