chr6-138843003-G-C

Variant names:

• chr6-138843003-G-C
• rs778851362
• NM_001077706.3:c.367G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077706.3(ECT2L):​c.367G>C​(p.Val123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07669172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.367G>C	p.Val123Leu	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.367G>C	p.Val123Leu	missense_variant	Exon 6 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.367G>C	p.Val123Leu	missense_variant	Exon 5 of 21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397476 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000828

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000283 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.14
DANN	Benign	0.87
DEOGEN2	Benign	0.0012	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	.;.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.045	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.15	N;N;.
REVEL	Benign	0.061
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.088	B;B;B
Vest4		0.21
MutPred		0.49		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.35
MPC		0.13
ClinPred		0.16	T
GERP RS		-3.9
Varity_R		0.053
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs778851362; hg19: chr6-139164140;