6-138813286-C-A

Variant names:

• chr6-138813286-C-A
• rs79219465
• NM_001077706.3:c.12C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077706.3(ECT2L):​c.12C>A​(p.Phe4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,612,132 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (75 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (72 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.380
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022556484).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	NM_001077706.3	MANE Select	c.12C>A	p.Phe4Leu	missense	Exon 3 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.12C>A	p.Phe4Leu	missense	Exon 2 of 21	NP_001181966.1	Q008S8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.12C>A	p.Phe4Leu	missense	Exon 3 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.12C>A	p.Phe4Leu	missense	Exon 2 of 21	ENSP00000356655.2	Q008S8
	ECT2L	ENST00000401414.4	TSL:4	c.12C>A	p.Phe4Leu	missense	Exon 2 of 3	ENSP00000385187.3	B7ZBI6

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2451 AN: 152122 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00417 AC: 1032 AN: 247542 AF XY: 0.00314

Gnomad AFR exome AF: 0.0602

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.00159 AC: 2325 AN: 1459892 Hom.: 72 Cov.: 29 AF XY: 0.00139 AC XY: 1013 AN XY: 726200

African (AFR) AF: 0.0586 AC: 1953 AN: 33314

American (AMR) AF: 0.00219 AC: 97 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111560

Other (OTH) AF: 0.00308 AC: 186 AN: 60314

GnomAD4 genome AF: 0.0161 AC: 2453 AN: 152240 Hom.: 75 Cov.: 33 AF XY: 0.0154 AC XY: 1147 AN XY: 74442

African (AFR) AF: 0.0553 AC: 2297 AN: 41542

American (AMR) AF: 0.00667 AC: 102 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68016

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.00632 Hom.: 40

Bravo AF: 0.0192

ESP6500AA AF: 0.0598 AC: 220

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00515 AC: 622

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.38
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.11
Sift	Benign	0.33	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.13		Gain of helix (P = 0.0854)
MVP		0.40
MPC		0.10
ClinPred		0.015	T
GERP RS		0.69
Varity_R		0.058
gMVP		0.16
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79219465; hg19: chr6-139134423;