Variant 3-186080081-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004454.3(ETV5):c.386C>G(p.Ser129Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000222 in 1,348,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 1 hom. )

Consequence

ETV5
NM_004454.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Variant links:

Genes affected

ETV5 (HGNC:3494): (ETS variant transcription factor 5) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ETV5 links:

ETV5-AS1 (HGNC:40222): (ETV5 antisense RNA 1)

ETV5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22555622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV5	NM_004454.3 linkuse as main transcript	c.386C>G	p.Ser129Cys	missense_variant	7/13	ENST00000306376.10	NP_004445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV5	ENST00000306376.10 linkuse as main transcript	c.386C>G	p.Ser129Cys	missense_variant	7/13	1	NM_004454.3	ENSP00000306894	P1	P41161-1
ETV5-AS1	ENST00000453370.1 linkuse as main transcript	n.173-479G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

152380

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

83560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000177

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000222

AC:

AN:

1348846

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

662750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000855

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.:

ExAC

AF:

0.0000166

AC:

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

Feb 27, 2024

The c.386C>G (p.S129C) alteration is located in exon 7 (coding exon 6) of the ETV5 gene. This alteration results from a C to G substitution at nucleotide position 386, causing the serine (S) at amino acid position 129 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

Benign

0.074

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;T;T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

.;T;T;T;D

M_CAP

Benign

0.0088

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.;.;.

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.058

T;T;T;D;T

Sift4G

Uncertain

0.023

D;D;T;T;.

Polyphen

0.93

P;P;.;.;.

Vest4

0.31

MutPred

0.44

Loss of glycosylation at S129 (P = 0.002);Loss of glycosylation at S129 (P = 0.002);Loss of glycosylation at S129 (P = 0.002);Loss of glycosylation at S129 (P = 0.002);Loss of glycosylation at S129 (P = 0.002);

MVP

0.30

MPC

0.45

ClinPred

0.54

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.53

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