6-138814569-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001077706.3(ECT2L):​c.145G>A​(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,611,060 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0073 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 15 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

18

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.427
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002331078).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00728 (1108/152098) while in subpopulation AFR AF= 0.0254 (1054/41470). AF 95% confidence interval is 0.0241. There are 17 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ECT2LNM_001077706.3 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 4/22 ENST00000541398.7 NP_001071174.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ECT2LENST00000541398.7 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 4/225 NM_001077706.3 ENSP00000442307 P1
ECT2LENST00000367682.6 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 3/215 ENSP00000356655 P1
ECT2LENST00000401414.4 linkuse as main transcriptc.145G>A p.Ala49Thr missense_variant 3/34 ENSP00000385187

Frequencies

GnomAD3 genomes
AF:
0.00727
AC:
1105
AN:
151980
Hom.:
17
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0254
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00230
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00201
AC:
501
AN:
248934
Hom.:
9
AF XY:
0.00158
AC XY:
213
AN XY:
135106
show subpopulations
Gnomad AFR exome
AF:
0.0288
Gnomad AMR exome
AF:
0.000957
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000390
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000797
Gnomad OTH exome
AF:
0.000829
GnomAD4 exome
AF:
0.000699
AC:
1020
AN:
1458962
Hom.:
15
Cov.:
30
AF XY:
0.000593
AC XY:
430
AN XY:
725674
show subpopulations
Gnomad4 AFR exome
AF:
0.0253
Gnomad4 AMR exome
AF:
0.00134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00143
GnomAD4 genome
AF:
0.00728
AC:
1108
AN:
152098
Hom.:
17
Cov.:
32
AF XY:
0.00720
AC XY:
535
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0254
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.000849
Hom.:
1
Bravo
AF:
0.00811
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0231
AC:
84
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00246
AC:
297
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
0.18
DANN
Benign
0.79
DEOGEN2
Benign
0.0020
T;T;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0098
N
LIST_S2
Benign
0.12
.;.;T;T
MetaRNN
Benign
0.0023
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.8
N;N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
1.0
N;N;.;N
REVEL
Benign
0.070
Sift
Benign
0.49
T;T;.;T
Sift4G
Benign
0.61
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.11
MVP
0.15
MPC
0.083
ClinPred
0.0022
T
GERP RS
0.21
Varity_R
0.017
gMVP
0.048

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs146769748; hg19: chr6-139135706; API