Variant 6-36366942-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000340181.9(ETV7):c.841C>T(p.Arg281Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R281H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

ETV7
ENST00000340181.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

ETV7 (HGNC:18160): (ETS variant transcription factor 7) The protein encoded by this gene belongs to the ETS family of transcription factors, which is a large group of evolutionarily conserved transcriptional regulators that play an important role in a variety of cellular processes throughout development and differentiation, and are involved in oncogenesis as well. This protein is predominantly expressed in hematopoietic tissues. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene (PMID:11108721).[provided by RefSeq, May 2011]

ETV7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV7	NM_016135.4 linkuse as main transcript	c.841C>T	p.Arg281Cys	missense_variant	7/8	ENST00000340181.9	NP_057219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV7	ENST00000340181.9 linkuse as main transcript	c.841C>T	p.Arg281Cys	missense_variant	7/8	1	NM_016135.4	ENSP00000341843	P2	Q9Y603-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.000176

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000755

AC:

AN:

251490

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000112

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000191

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.841C>T (p.R281C) alteration is located in exon 7 (coding exon 7) of the ETV7 gene. This alteration results from a C to T substitution at nucleotide position 841, causing the arginine (R) at amino acid position 281 to be replaced by a cysteine (C). 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

0.99

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

.;.;D;.;.;.;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

1.0

D;D;D;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.4

M;.;M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-7.9

D;.;D;D;D;.;.;D

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;.;D;D;D;.;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;.;D;.

Vest4

0.86

MVP

0.72

MPC

0.89

ClinPred

0.94

GERP RS

3.6

Varity_R

0.92

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over