rs1023611673

Variant names:

• chr6-138843033-C-T
• rs1023611673
• NM_001077706.3:c.397C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077706.3(ECT2L):​c.397C>T​(p.Pro133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36414614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.397C>T	p.Pro133Ser	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.397C>T	p.Pro133Ser	missense_variant	Exon 6 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.397C>T	p.Pro133Ser	missense_variant	Exon 5 of 21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.397C>T (p.P133S) alteration is located in exon 6 (coding exon 4) of the ECT2L gene. This alteration results from a C to T substitution at nucleotide position 397, causing the proline (P) at amino acid position 133 to be replaced by a serine (S). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.099	T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	.;.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.9	D;D;.
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.80	P;P;P
Vest4		0.36
MutPred		0.60		Gain of catalytic residue at P133 (P = 0.0247);Gain of catalytic residue at P133 (P = 0.0247);Gain of catalytic residue at P133 (P = 0.0247);
MVP		0.41
MPC		0.47
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.46
gMVP		0.54

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: rs1023611673; hg19: chr6-139164170;