Variant 12-96247343-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005230.4(ELK3):c.611C>T(p.Thr204Met) variant causes a missense change. The variant allele was found at a frequency of 0.00278 in 1,614,206 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 8 hom. )

Consequence

ELK3
NM_005230.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.76

Variant links:

Genes affected

ELK3 (HGNC:3325): (ETS transcription factor ELK3) This gene encodes a member of the ETS-domain transcription factor family and the ternary complex factor (TCF) subfamily. Proteins in this subfamily regulate transcription when recruited by serum response factor to bind to serum response elements. This protein is activated by signal-induced phosphorylation; studies in rodents suggest that it is a transcriptional inhibitor in the absence of Ras, but activates transcription when Ras is present. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ELK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011483699).

BP6

Variant 12-96247343-C-T is Benign according to our data. Variant chr12-96247343-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELK3	NM_005230.4 linkuse as main transcript	c.611C>T	p.Thr204Met	missense_variant	3/5	ENST00000228741.8	NP_005221.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ELK3	ENST00000228741.8 linkuse as main transcript	c.611C>T	p.Thr204Met	missense_variant	3/5	1	NM_005230.4	ENSP00000228741	P1
ELK3	ENST00000552142.5 linkuse as main transcript	c.208-12388C>T		intron_variant		5		ENSP00000449430
ELK3	ENST00000549985.1 linkuse as main transcript	c.153+60C>T		intron_variant, NMD_transcript_variant		3		ENSP00000449420

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

311

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00345

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00209

AC:

525

AN:

251382

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00285

AC:

4171

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2041

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00344

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00205

AC:

312

AN:

152344

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00247

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00189

AC:

230

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.031

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

REVEL

Benign

0.13

Sift

Uncertain

0.012

Sift4G

Benign

0.097

Polyphen

0.99

Vest4

0.48

MVP

0.79

MPC

0.84

ClinPred

0.029

GERP RS

5.7

Varity_R

0.096

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over