Variant 12-96247410-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005230.4(ELK3):c.678G>A(p.Met226Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00219 in 1,614,076 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

ELK3
NM_005230.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.25

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013999373).

BP6

Variant 12-96247410-G-A is Benign according to our data. Variant chr12-96247410-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709509.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELK3	NM_005230.4 linkuse as main transcript	c.678G>A	p.Met226Ile	missense_variant	3/5	ENST00000228741.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ELK3	ENST00000228741.8 linkuse as main transcript	c.678G>A	p.Met226Ile	missense_variant	3/5	1	NM_005230.4	P1
ELK3	ENST00000552142.5 linkuse as main transcript	c.208-12321G>A		intron_variant		5
ELK3	ENST00000549985.1 linkuse as main transcript	c.153+127G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00149

AC:

374

AN:

251184

Hom.:

AF XY:

0.00138

AC XY:

188

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00290

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00231

AC:

3374

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1622

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000488

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152304

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00118

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00173

AC:

210

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

0.067

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

M_CAP

Benign

0.022

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.14

REVEL

Benign

0.12

Sift

Benign

0.23

Sift4G

Benign

0.19

Polyphen

0.13

Vest4

0.51

MutPred

0.33

Gain of catalytic residue at L227 (P = 5e-04);

MVP

0.56

MPC

0.25

ClinPred

0.011

GERP RS

5.5

Varity_R

0.25

gMVP

0.30

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