Variant chrX-47637806-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114123.3(ELK1):c.1031G>C(p.Gly344Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,193,617 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

ELK1
NM_001114123.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

ELK1 (HGNC:3321): (ETS transcription factor ELK1) This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is a nuclear target for the ras-raf-MAPK signaling cascade. This gene produces multiple isoforms by using alternative translational start codons and by alternative splicing. Related pseudogenes have been identified on chromosomes 7 and 14. [provided by RefSeq, Mar 2012]

ELK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057476014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELK1	NM_001114123.3 linkuse as main transcript	c.1031G>C	p.Gly344Ala	missense_variant	5/7	ENST00000376983.8
ELK1	NM_005229.4 linkuse as main transcript	c.1031G>C	p.Gly344Ala	missense_variant	4/6
ELK1	NM_001257168.1 linkuse as main transcript	c.271-754G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELK1	ENST00000376983.8 linkuse as main transcript	c.1031G>C	p.Gly344Ala	missense_variant	5/7	1	NM_001114123.3	P1	P19419-1
ELK1	ENST00000247161.7 linkuse as main transcript	c.1031G>C	p.Gly344Ala	missense_variant	4/6	1		P1	P19419-1
ELK1	ENST00000343894.8 linkuse as main transcript	c.271-754G>C		intron_variant		1			P19419-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112370

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34526

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000564

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

146513

Hom.:

AF XY:

0.00

AC XY:

AN XY:

45771

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS 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:

0.0000129

AC:

AN:

1081247

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

351379

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000169

Gnomad4 SAS exome

AF:

0.0000192

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000177

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112370

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34526

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000564

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000336

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.1031G>C (p.G344A) alteration is located in exon 4 (coding exon 3) of the ELK1 gene. This alteration results from a G to C substitution at nucleotide position 1031, causing the glycine (G) at amino acid position 344 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

FATHMM_MKL

Benign

0.54

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.73

D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.032

Sift

Benign

0.079

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.16

B;B

Vest4

0.28

MutPred

0.13

Loss of glycosylation at S343 (P = 0.098);Loss of glycosylation at S343 (P = 0.098);

MVP

0.33

MPC

0.37

ClinPred

0.076

GERP RS

5.5

Varity_R

0.15

gMVP

0.46

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