rs300239

chr5-74634926-C-Gchr5-74634926-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ENC1
• BP4: Computational evidence support a benign effect (MetaRNN=0.4091256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENC1	NM_003633.4	c.1560G>C	p.Lys520Asn	missense_variant	2/3	ENST00000302351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENC1	ENST00000302351.9	c.1560G>C	p.Lys520Asn	missense_variant	2/3	1	NM_003633.4	P1
ENC1	ENST00000618628.4	c.1560G>C	p.Lys520Asn	missense_variant	3/4	5		P1
ENC1	ENST00000651128.1	c.1560G>C	p.Lys520Asn	missense_variant	3/4			P1
ENC1	ENST00000510316.5	c.1341G>C	p.Lys447Asn	missense_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.5	L;L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.95	N;.;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D;.;D;D
Sift4G	Uncertain	0.043	D;D;D;D
Polyphen		0.60	P;P;.;P
Vest4		0.58
MutPred		0.42		Loss of methylation at K520 (P = 0.0171);Loss of methylation at K520 (P = 0.0171);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs300239; hg19: chr5-73930751;