ETV4 p.Phe317Leu

Variant names:

• chr17-43529888-A-T
• NM_001079675.5:c.951T>A
• ETV4 p.Phe317Leu

Your query was ambiguous. Multiple possible variants found:

• chr17-43529888-A-T
• chr17-43529888-A-C
• chr17-43529890-A-G
• chr17-43529888-AAA-GAG
• chr17-43529888-AAA-TAG
• chr17-43529888-AAA-CAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001079675.5(ETV4):​c.951T>A​(p.Phe317Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ETV4 NM_001079675.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

ETV4 (HGNC:3493): (ETS variant transcription factor 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1044288).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079675.5. 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
	ETV4	NM_001079675.5	MANE Select	c.951T>A	p.Phe317Leu	missense	Exon 10 of 13	NP_001073143.1	P43268-1
	ETV4	NM_001369366.2		c.951T>A	p.Phe317Leu	missense	Exon 10 of 13	NP_001356295.1	P43268-1
	ETV4	NM_001986.4		c.951T>A	p.Phe317Leu	missense	Exon 10 of 13	NP_001977.1	P43268-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	ENST00000319349.10	TSL:1 MANE Select	c.951T>A	p.Phe317Leu	missense	Exon 10 of 13	ENSP00000321835.4	P43268-1
	ETV4	ENST00000393664.6	TSL:1	c.951T>A	p.Phe317Leu	missense	Exon 9 of 12	ENSP00000377273.1	P43268-1
	ETV4	ENST00000591713.5	TSL:1	c.951T>A	p.Phe317Leu	missense	Exon 10 of 13	ENSP00000465718.1	P43268-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.71
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		1.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Benign	0.75	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-41607256;