1-160213167-C-G

Variant names:

• chr1-160213167-C-G
• rs1654945451
• NM_003768.5:c.230C>G

Variant summary

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

The NM_003768.5(PEA15):​c.230C>G​(p.Thr77Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T77I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEA15 NM_003768.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.230C>G	p.Thr77Ser	missense	Exon 3 of 4	NP_003759.1	Q15121-1
	PEA15	NM_001297576.2		c.293C>G	p.Thr98Ser	missense	Exon 5 of 6	NP_001284505.1	Q15121-2
	PEA15	NM_001297577.2		c.230C>G	p.Thr77Ser	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.230C>G	p.Thr77Ser	missense	Exon 3 of 4	ENSP00000353660.5	Q15121-1
	PEA15	ENST00000368076.1	TSL:2	c.293C>G	p.Thr98Ser	missense	Exon 5 of 6	ENSP00000357055.1	Q15121-2
	PEA15	ENST00000853680.1		c.230C>G	p.Thr77Ser	missense	Exon 4 of 5	ENSP00000523739.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.70	N
REVEL	Uncertain	0.48
Sift	Benign	0.14	T
Sift4G	Benign	0.29	T
Polyphen		0.89	P
Vest4		0.53
MutPred		0.50		Loss of sheet (P = 0.0084)
MVP		0.80
MPC		2.3
ClinPred		0.81	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.46
Mutation Taster		=31/69	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: rs1654945451; hg19: chr1-160182957;