ENC1 p.Lys520Lys

Variant names:

• chr5-74634925-C-C
• NM_003633.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-74634926--
• chr5-74634926-C-T

Variant summary

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

The NM_003633.4(ENC1):​c. variant causes a exon region change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENC1 NM_003633.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 0 publications found

Genes affected

ENC1 (HGNC:3345): (ectodermal-neural cortex 1) This gene encodes a member of the kelch-related family of actin-binding proteins. The encoded protein plays a role in the oxidative stress response as a regulator of the transcription factor Nrf2, and expression of this gene may play a role in malignant transformation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

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_003633.4. 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
	ENC1	NM_003633.4	MANE Select	c.		exon_region	Exon 2 of 3	NP_003624.1	Q53XS2
	ENC1	NM_001256574.2		c.		exon_region	Exon 3 of 4	NP_001243503.1	O14682-1
	ENC1	NM_001256575.2		c.		exon_region	Exon 3 of 4	NP_001243504.1	Q53XS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENC1	ENST00000302351.9	TSL:1 MANE Select	c.		exon_region	Exon 2 of 3	ENSP00000306356.4	O14682-1
	ENC1	ENST00000618628.4	TSL:5	c.		exon_region	Exon 3 of 4	ENSP00000479101.1	O14682-1
	ENC1	ENST00000651128.1		c.		exon_region	Exon 3 of 4	ENSP00000499185.1	O14682-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78

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: chr5-73930750;