chr1-157092701-G-C

Variant names:

• chr1-157092701-G-C
• rs540393763
• NM_001004341.2:c.1034C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004341.2(ETV3L):​c.1034C>G​(p.Thr345Ser) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T345I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETV3L NM_001004341.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034260362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV3L	NM_001004341.2	c.1034C>G	p.Thr345Ser	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.1034C>G	p.Thr345Ser	missense_variant	Exon 5 of 5	2	NM_001004341.2	ENSP00000430271.1
ETV3L	ENST00000671886.1	c.1034C>G	p.Thr345Ser	missense_variant	Exon 6 of 6			ENSP00000500322.1
ETV3L	ENST00000671942.1	c.1034C>G	p.Thr345Ser	missense_variant	Exon 6 of 6			ENSP00000500028.1
ETV3L	ENST00000672100.1	c.1034C>G	p.Thr345Ser	missense_variant	Exon 6 of 6			ENSP00000500154.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0030
DANN	Benign	0.58
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-3.0
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.031
Sift	Benign	0.29	T
Sift4G	Benign	0.46	T
Polyphen		0.0090	B
Vest4		0.053
MutPred		0.16		Gain of phosphorylation at T345 (P = 0.0732);
MVP		0.10
MPC		0.025
ClinPred		0.69	D
GERP RS		-8.6
Varity_R		0.044
gMVP		0.023
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs540393763; hg19: chr1-157062493;