1-157093050-C-A

Variant names:

• chr1-157093050-C-A
• rs868738637
• NM_001004341.2:c.685G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001004341.2(ETV3L):​c.685G>T​(p.Val229Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,404,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ETV3L NM_001004341.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

Genes affected

ETV3L (HGNC:33834): (ETS variant transcription factor 3 like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027805805).
• BP6: Variant 1-157093050-C-A is Benign according to our data. Variant chr1-157093050-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2337603.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV3L	NM_001004341.2	c.685G>T	p.Val229Phe	missense_variant	Exon 5 of 5	ENST00000454449.3	NP_001004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV3L	ENST00000454449.3	c.685G>T	p.Val229Phe	missense_variant	Exon 5 of 5	2	NM_001004341.2	ENSP00000430271.1
ETV3L	ENST00000671886.1	c.685G>T	p.Val229Phe	missense_variant	Exon 6 of 6			ENSP00000500322.1
ETV3L	ENST00000671942.1	c.685G>T	p.Val229Phe	missense_variant	Exon 6 of 6			ENSP00000500028.1
ETV3L	ENST00000672100.1	c.685G>T	p.Val229Phe	missense_variant	Exon 6 of 6			ENSP00000500154.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1404134 Hom.: 0 Cov.: 33 AF XY: 0.00000289 AC XY: 2 AN XY: 692960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000274

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 19, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.81
DEOGEN2	Benign	0.00033	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.71	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.0050
Sift	Benign	0.79	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.17		Loss of sheet (P = 0.1158);
MVP		0.085
MPC		0.031
ClinPred		0.032	T
GERP RS		-1.3
Varity_R		0.031
gMVP		0.078

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: rs868738637; hg19: chr1-157062842;