3-186066019-A-G

Variant summary

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

The NM_004454.3(ETV5):c.704T>C(p.Val235Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ETV5 NM_004454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31

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]

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=0.10497463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.704T>C	p.Val235Ala	missense_variant	8/13	ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.704T>C	p.Val235Ala	missense_variant	8/13	1	NM_004454.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.704T>C (p.V235A) alteration is located in exon 8 (coding exon 7) of the ETV5 gene. This alteration results from a T to C substitution at nucleotide position 704, causing the valine (V) at amino acid position 235 to be replaced by an alanine (A). 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	0.093
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	20
Dann	Benign	0.96
DEOGEN2	Benign	0.056	T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.56	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N;N
MutationTaster	Benign	0.62	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.054
Sift	Benign	0.67	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.059	B;B
Vest4		0.35
MutPred		0.31		Gain of glycosylation at P230 (P = 0.1128);Gain of glycosylation at P230 (P = 0.1128);
MVP		0.53
MPC		0.31
ClinPred		0.70	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-185783808;