rs137969667

Variant names:

• chr17-43530116-C-A
• rs137969667
• NM_001079675.5:c.877G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-43530116-C-A
• chr17-43530116-C-G
• chr17-43530116-C-T

Variant summary

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

The NM_001079675.5(ETV4):​c.877G>T​(p.Gly293Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,432,618 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: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ETV4 NM_001079675.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.606
• Publications: 1 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 2 ACMG points.

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

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.877G>T	p.Gly293Trp	missense	Exon 9 of 13	NP_001073143.1	P43268-1
	ETV4	NM_001369366.2		c.877G>T	p.Gly293Trp	missense	Exon 9 of 13	NP_001356295.1	P43268-1
	ETV4	NM_001986.4		c.877G>T	p.Gly293Trp	missense	Exon 9 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.877G>T	p.Gly293Trp	missense	Exon 9 of 13	ENSP00000321835.4	P43268-1
	ETV4	ENST00000393664.6	TSL:1	c.877G>T	p.Gly293Trp	missense	Exon 8 of 12	ENSP00000377273.1	P43268-1
	ETV4	ENST00000591713.5	TSL:1	c.877G>T	p.Gly293Trp	missense	Exon 9 of 13	ENSP00000465718.1	P43268-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000303 AC: 6 AN: 198222 AF XY: 0.0000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 16 AN: 1432618 Hom.: 0 Cov.: 32 AF XY: 0.0000169 AC XY: 12 AN XY: 710446

African (AFR) AF: 0.00 AC: 0 AN: 32602

American (AMR) AF: 0.00 AC: 0 AN: 38610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 37720

South Asian (SAS) AF: 0.000155 AC: 13 AN: 83786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51918

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097170

Other (OTH) AF: 0.00 AC: 0 AN: 59410

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000508 AC: 6

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	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.61
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.089
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.14	T
Polyphen		0.83	P
Vest4		0.36
MutPred		0.63		Loss of disorder (P = 0.0028)
MVP		0.34
MPC		0.99
ClinPred		0.39	T
GERP RS		1.0
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.52
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 6

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

Other links and lift over

dbSNP: rs137969667; hg19: chr17-41607484;