3-186080012-G-T

Variant names:

• chr3-186080012-G-T
• rs537105512
• NM_004454.3:c.455C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_004454.3(ETV5):​c.455C>A​(p.Pro152Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000722 in 1,550,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: ETV5 NM_004454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.04
• Publications: 1 publications found

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)

LOC124909470 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21762297).
• BS2: High AC in GnomAd4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	NM_004454.3	MANE Select	c.455C>A	p.Pro152Gln	missense	Exon 7 of 13	NP_004445.1	P41161-1
	ETV5-AS1	NR_046594.1		n.173-548G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	ENST00000306376.10	TSL:1 MANE Select	c.455C>A	p.Pro152Gln	missense	Exon 7 of 13	ENSP00000306894.5	P41161-1
	ETV5	ENST00000434744.5	TSL:1	c.455C>A	p.Pro152Gln	missense	Exon 7 of 13	ENSP00000413755.1	P41161-1
	ETV5	ENST00000875747.1		c.455C>A	p.Pro152Gln	missense	Exon 7 of 13	ENSP00000545806.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000994 AC: 19 AN: 191180 AF XY: 0.000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000105

Gnomad ASJ exome AF: 0.000133

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000492

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000230

GnomAD4 exome AF: 0.0000730 AC: 102 AN: 1398086 Hom.: 0 Cov.: 36 AF XY: 0.0000736 AC XY: 51 AN XY: 693014

African (AFR) AF: 0.000102 AC: 3 AN: 29448

American (AMR) AF: 0.000170 AC: 5 AN: 29402

Ashkenazi Jewish (ASJ) AF: 0.0000419 AC: 1 AN: 23844

East Asian (EAS) AF: 0.00 AC: 0 AN: 36352

South Asian (SAS) AF: 0.0000272 AC: 2 AN: 73522

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52730

Middle Eastern (MID) AF: 0.000745 AC: 4 AN: 5368

European-Non Finnish (NFE) AF: 0.0000707 AC: 77 AN: 1089534

Other (OTH) AF: 0.000138 AC: 8 AN: 57886

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74420

African (AFR) AF: 0.0000241 AC: 1 AN: 41496

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000205 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.000116 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.097
Sift	Benign	0.097	T
Sift4G	Uncertain	0.049	D
Polyphen		0.62	P
Vest4		0.52
MutPred		0.34		Loss of glycosylation at P152 (P = 0.0056)
MVP		0.29
MPC		0.74
ClinPred		0.13	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.37
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs537105512; hg19: chr3-185797801; COSMIC: COSV60500242;