NM_003633.4:c.1560G>C

Variant names:

• chr5-74634926-C-G
• rs300239
• NM_003633.4:c.1560G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003633.4(ENC1):​c.1560G>C​(p.Lys520Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 20 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4091256).

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.1560G>C	p.Lys520Asn	missense	Exon 2 of 3	NP_003624.1	Q53XS2
	ENC1	NM_001256574.2		c.1560G>C	p.Lys520Asn	missense	Exon 3 of 4	NP_001243503.1	O14682-1
	ENC1	NM_001256575.2		c.1560G>C	p.Lys520Asn	missense	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.1560G>C	p.Lys520Asn	missense	Exon 2 of 3	ENSP00000306356.4	O14682-1
	ENC1	ENST00000618628.4	TSL:5	c.1560G>C	p.Lys520Asn	missense	Exon 3 of 4	ENSP00000479101.1	O14682-1
	ENC1	ENST00000651128.1		c.1560G>C	p.Lys520Asn	missense	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
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.78
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.043	D
Polyphen		0.60	P
Vest4		0.58
MutPred		0.42		Loss of methylation at K520 (P = 0.0171)
MVP		0.51
MPC		1.8
ClinPred		0.80	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
Mutation Taster		=55/45	polymorphism

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: rs300239; hg19: chr5-73930751;