19-16395450-ATT-GTG

Variant names:

• chr19-16395450-ATT-GTG
• NM_001258374.3:c.1807_1809delAATinsCAC
• EPS15L1 p.Asn603His

Variant summary

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

The NM_001258374.3(EPS15L1):​c.1807_1809delAATinsCAC​(p.Asn603His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EPS15L1 NM_001258374.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

Genes affected

EPS15L1 (HGNC:24634): (epidermal growth factor receptor pathway substrate 15 like 1) Enables cadherin binding activity. Predicted to be involved in endocytosis and endosomal transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPS15L1 Gene-Disease associations (from GenCC):

• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258374.3. 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
	EPS15L1	NM_001258374.3	MANE Select	c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	NP_001245303.1	Q9UBC2-2
	EPS15L1	NM_001438224.1		c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	NP_001425153.1
	EPS15L1	NM_021235.3		c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	NP_067058.1	Q9UBC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15L1	ENST00000455140.7	TSL:2 MANE Select	c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	ENSP00000393313.1	Q9UBC2-2
	EPS15L1	ENST00000248070.10	TSL:1	c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	ENSP00000248070.5	Q9UBC2-1
	EPS15L1	ENST00000535753.6	TSL:1	c.1807_1809delAATinsCAC	p.Asn603His	missense	N/A	ENSP00000440103.1	Q9UBC2-3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-16506261;