6-138849416-G-T

Variant names:

• chr6-138849416-G-T
• rs73557274
• NM_001077706.3:c.1051G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001077706.3(ECT2L):​c.1051G>T​(p.Glu351*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,613,490 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00086 (2 hom.)
• Consequence: ECT2L NM_001077706.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.1051G>T	p.Glu351*	stop_gained	Exon 9 of 22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.1051G>T	p.Glu351*	stop_gained	Exon 9 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.1051G>T	p.Glu351*	stop_gained	Exon 8 of 21	5		ENSP00000356655.2
ECT2L	ENST00000495970.1	n.39G>T		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.000585 AC: 89 AN: 152086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000620 AC: 154 AN: 248584 Hom.: 0 AF XY: 0.000630 AC XY: 85 AN XY: 134888

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000409

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000830

GnomAD4 exome AF: 0.000859 AC: 1255 AN: 1461284 Hom.: 2 Cov.: 30 AF XY: 0.000841 AC XY: 611 AN XY: 726932

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000381

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.000585 AC: 89 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000524 AC XY: 39 AN XY: 74428

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000738 Hom.: 7

Bravo AF: 0.000574

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.000554 AC: 67

EpiCase AF: 0.000874

EpiControl AF: 0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Uncertain	0.90	D
Vest4		0.20
GERP RS		5.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73557274; hg19: chr6-139170553;