3-186079931-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5 BP4 BS2

The NM_004454.3(ETV5):c.536A>C(p.His179Pro) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETV5 NM_004454.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.20

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PP5: Variant 3-186079931-T-G is Pathogenic according to our data. Variant chr3-186079931-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1801782.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.07760486).. Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAdExome at 225 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.536A>C	p.His179Pro	missense_variant	7/13	ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.536A>C	p.His179Pro	missense_variant	7/13	1	NM_004454.3	P1
ETV5-AS1	ENST00000453370.1	n.172+590T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 136 AN: 14064 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.0192

Gnomad AMR AF: 0.00774

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00643

Gnomad SAS AF: 0.0121

Gnomad FIN AF: 0.00542

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00877

GnomAD3 exomes AF: 0.00143 AC: 225 AN: 157416 Hom.: 0 AF XY: 0.00143 AC XY: 126 AN XY: 88122

Gnomad AFR exome AF: 0.000578

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00320

Gnomad EAS exome AF: 0.000593

Gnomad SAS exome AF: 0.00221

Gnomad FIN exome AF: 0.00209

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00269

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0175 AC: 3570 AN: 204310 Hom.: 0 Cov.: 0 AF XY: 0.0184 AC XY: 2064 AN XY: 112290

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.00713

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.00468

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00964 AC: 136 AN: 14106 Hom.: 0 Cov.: 0 AF XY: 0.00941 AC XY: 68 AN XY: 7228

Gnomad4 AFR AF: 0.00943

Gnomad4 AMR AF: 0.00769

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00641

Gnomad4 SAS AF: 0.0121

Gnomad4 FIN AF: 0.00542

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00855

Alfa AF: 0.0602 Hom.: 0

ExAC AF: 0.000124 AC: 15

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myoepithelial tumor Pathogenic:1

Pathogenic, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	19
Dann	Benign	0.93
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Benign	0.049	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.0	B;B
Vest4		0.65
MutPred		0.40		Gain of glycosylation at H179 (P = 0.0037);Gain of glycosylation at H179 (P = 0.0037);
MVP		0.62
MPC		0.48
ClinPred		0.020	T
GERP RS		5.3
Varity_R		0.34
gMVP		0.33

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

Other links and lift over

dbSNP: rs772183700; hg19: chr3-185797720; COSMIC: COSV60503906; COSMIC: COSV60503906;