1-157093050-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001004341.2(ETV3L):​c.685G>T​(p.Val229Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,404,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ETV3L
NM_001004341.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410
Variant links:
Genes affected
ETV3L (HGNC:33834): (ETS variant transcription factor 3 like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027805805).
BP6
Variant 1-157093050-C-A is Benign according to our data. Variant chr1-157093050-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2337603.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ETV3LNM_001004341.2 linkc.685G>T p.Val229Phe missense_variant Exon 5 of 5 ENST00000454449.3 NP_001004341.1 Q6ZN32

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ETV3LENST00000454449.3 linkc.685G>T p.Val229Phe missense_variant Exon 5 of 5 2 NM_001004341.2 ENSP00000430271.1 Q6ZN32
ETV3LENST00000671886.1 linkc.685G>T p.Val229Phe missense_variant Exon 6 of 6 ENSP00000500322.1 Q6ZN32
ETV3LENST00000671942.1 linkc.685G>T p.Val229Phe missense_variant Exon 6 of 6 ENSP00000500028.1 Q6ZN32
ETV3LENST00000672100.1 linkc.685G>T p.Val229Phe missense_variant Exon 6 of 6 ENSP00000500154.1 Q6ZN32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000285
AC:
4
AN:
1404134
Hom.:
0
Cov.:
33
AF XY:
0.00000289
AC XY:
2
AN XY:
692960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000274
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000277
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 19, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.14
DANN
Benign
0.81
DEOGEN2
Benign
0.00033
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0032
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.028
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.71
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.21
N
REVEL
Benign
0.0050
Sift
Benign
0.79
T
Sift4G
Benign
0.70
T
Polyphen
0.0
B
Vest4
0.050
MutPred
0.17
Loss of sheet (P = 0.1158);
MVP
0.085
MPC
0.031
ClinPred
0.032
T
GERP RS
-1.3
Varity_R
0.031
gMVP
0.078

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.

Other links and lift over

dbSNP: rs868738637; hg19: chr1-157062842; API