Variant 6-138813326-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077706.3(ECT2L):c.52T>C(p.Ser18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

Variant links:

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]

ECT2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0707182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 linkuse as main transcript	c.52T>C	p.Ser18Pro	missense_variant	3/22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ECT2L	ENST00000541398.7 linkuse as main transcript	c.52T>C	p.Ser18Pro	missense_variant	3/22	5	NM_001077706.3	ENSP00000442307	P1
ECT2L	ENST00000367682.6 linkuse as main transcript	c.52T>C	p.Ser18Pro	missense_variant	2/21	5		ENSP00000356655	P1
ECT2L	ENST00000401414.4 linkuse as main transcript	c.52T>C	p.Ser18Pro	missense_variant	2/3	4		ENSP00000385187

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725684

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.52T>C (p.S18P) alteration is located in exon 3 (coding exon 1) of the ECT2L gene. This alteration results from a T to C substitution at nucleotide position 52, causing the serine (S) at amino acid position 18 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.2

DANN

Benign

0.84

DEOGEN2

Benign

0.0011

T;T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.42

.;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.071

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;.

MutationTaster

Benign

0.86

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.15

N;N;.;N

REVEL

Benign

0.052

Sift

Benign

0.33

T;T;.;T

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.0040

B;B;B;.

Vest4

0.14

MutPred

0.36

Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);

MVP

0.25

MPC

0.12

ClinPred

0.058

GERP RS

-0.40

Varity_R

0.055

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over