NM_001077706.3:c.1739A>T

Variant names:

• chr6-138881030-A-T
• rs587778240
• NM_001077706.3:c.1739A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077706.3(ECT2L):​c.1739A>T​(p.Lys580Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K580R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24651411).

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.1739A>T	p.Lys580Ile	missense	Exon 15 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.1739A>T	p.Lys580Ile	missense	Exon 14 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.1739A>T	p.Lys580Ile	missense	Exon 15 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.1739A>T	p.Lys580Ile	missense	Exon 14 of 21	ENSP00000356655.2	Q008S8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152304 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74470

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.11
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.26
Sift	Benign	0.14	T
Sift4G	Uncertain	0.059	T
Polyphen		0.78	P
Vest4		0.43
MutPred		0.62		Loss of ubiquitination at K580 (P = 0.0326)
MVP		0.38
MPC		0.16
ClinPred		0.46	T
GERP RS		-0.85
Varity_R		0.12
gMVP		0.32
Mutation Taster		=93/7	polymorphism

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: rs587778240; hg19: chr6-139202167;