17-43529628-T-G

Variant names:

• chr17-43529628-T-G
• rs1567706269
• NM_001079675.5:c.1004A>C

Variant summary

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

The NM_001079675.5(ETV4):​c.1004A>C​(p.Tyr335Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ETV4 NM_001079675.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV4	NM_001079675.5	c.1004A>C	p.Tyr335Ser	missense_variant	Exon 11 of 13	ENST00000319349.10	NP_001073143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10	c.1004A>C	p.Tyr335Ser	missense_variant	Exon 11 of 13	1	NM_001079675.5	ENSP00000321835.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	.;T;T;.;T;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;.;.;.;D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	.;M;M;.;.;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-8.3	D;D;D;D;D;.;.
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D;D;D;D;D;.;.
Sift4G	Uncertain	0.057	T;D;D;T;D;D;T
Polyphen		0.99, 0.89	.;D;D;.;P;D;.
Vest4		0.56
MutPred		0.63		.;Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);.;.;Gain of disorder (P = 0.0091);.;
MVP		0.86
MPC		1.0
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.74

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: rs1567706269; hg19: chr17-41606996;