1-160213151-C-T

Variant names:

• chr1-160213151-C-T
• rs1389761498
• NM_003768.5:c.214C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003768.5(PEA15):​c.214C>T​(p.Arg72Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEA15 NM_003768.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

Genes affected

PEA15 (HGNC:8822): (proliferation and apoptosis adaptor protein 15) This gene encodes a death effector domain-containing protein that functions as a negative regulator of apoptosis. The encoded protein is an endogenous substrate for protein kinase C. This protein is also overexpressed in type 2 diabetes mellitus, where it may contribute to insulin resistance in glucose uptake. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003768.5. 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
	PEA15	NM_003768.5	MANE Select	c.214C>T	p.Arg72Cys	missense	Exon 3 of 4	NP_003759.1	Q15121-1
	PEA15	NM_001297576.2		c.277C>T	p.Arg93Cys	missense	Exon 5 of 6	NP_001284505.1	Q15121-2
	PEA15	NM_001297577.2		c.214C>T	p.Arg72Cys	missense	Exon 4 of 5	NP_001284506.1	Q15121-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEA15	ENST00000360472.9	TSL:1 MANE Select	c.214C>T	p.Arg72Cys	missense	Exon 3 of 4	ENSP00000353660.5	Q15121-1
	PEA15	ENST00000368076.1	TSL:2	c.277C>T	p.Arg93Cys	missense	Exon 5 of 6	ENSP00000357055.1	Q15121-2
	PEA15	ENST00000853680.1		c.214C>T	p.Arg72Cys	missense	Exon 4 of 5	ENSP00000523739.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.94	D
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.97	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.84
Sift	Benign	0.058	T
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.90		Gain of sheet (P = 0.0477)
MVP		0.97
MPC		2.7
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.95
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1389761498; hg19: chr1-160182941;