6-138843018-T-G

Variant names:

• chr6-138843018-T-G
• rs1583580198
• NM_001077706.3:c.382T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001077706.3(ECT2L):​c.382T>G​(p.Phe128Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: ECT2L NM_001077706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

Genes affected

ECT2L (HGNC:21118): (epithelial cell transforming 2 like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.382T>G	p.Phe128Val	missense_variant	Exon 6 of 22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.382T>G	p.Phe128Val	missense_variant	Exon 6 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.382T>G	p.Phe128Val	missense_variant	Exon 5 of 21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T;T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.9	D;D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.75
MutPred		0.61		Loss of glycosylation at P133 (P = 0.1745);Loss of glycosylation at P133 (P = 0.1745);Loss of glycosylation at P133 (P = 0.1745);
MVP		0.46
MPC		0.54
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.74
gMVP		0.65

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: rs1583580198; hg19: chr6-139164155;