5-74635164-C-T

Position:

• chr5-74635164-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_003633.4(ENC1):​c.1322G>A​(p.Ser441Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENC1 NM_003633.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ENC1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENC1	NM_003633.4	c.1322G>A	p.Ser441Asn	missense_variant	2/3	ENST00000302351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENC1	ENST00000302351.9	c.1322G>A	p.Ser441Asn	missense_variant	2/3	1	NM_003633.4	P1
ENC1	ENST00000618628.4	c.1322G>A	p.Ser441Asn	missense_variant	3/4	5		P1
ENC1	ENST00000651128.1	c.1322G>A	p.Ser441Asn	missense_variant	3/4			P1
ENC1	ENST00000510316.5	c.1103G>A	p.Ser368Asn	missense_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;T;.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.2	M;M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N;.;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;.;D;D
Sift4G	Uncertain	0.045	D;D;T;D
Polyphen		0.027	B;B;.;B
Vest4		0.70
MutPred		0.48		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);
MVP		0.62
MPC		0.84
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-73930989;