NM_001981.3:c.1329C>A

Variant names:

• chr1-51408279-G-T
• rs1065754
• NM_001981.3:c.1329C>A

Variant summary

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

The NM_001981.3(EPS15):​c.1329C>A​(p.Tyr443*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPS15 NM_001981.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 28 publications found

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

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_001981.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15	NM_001981.3	MANE Select	c.1329C>A	p.Tyr443*	stop_gained	Exon 15 of 25	NP_001972.1
	EPS15	NM_001410797.1		c.1440C>A	p.Tyr480*	stop_gained	Exon 15 of 25	NP_001397726.1
	EPS15	NM_001410796.1		c.1239C>A	p.Tyr413*	stop_gained	Exon 14 of 24	NP_001397725.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15	ENST00000371733.8	TSL:1 MANE Select	c.1329C>A	p.Tyr443*	stop_gained	Exon 15 of 25	ENSP00000360798.3
	EPS15	ENST00000371730.6	TSL:1	c.1275+1256C>A		intron	N/A	ENSP00000360795.2
	EPS15	ENST00000706292.1		c.1440C>A	p.Tyr480*	stop_gained	Exon 15 of 25	ENSP00000516336.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.0099
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.22	N
PhyloP100		-0.67
Vest4		0.98
GERP RS		-1.7
Mutation Taster		=3/197	disease causing (fs/PTC)

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: rs1065754; hg19: chr1-51873951;