14-23359427-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005864.4(EFS):c.1051A>G(p.Lys351Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,335,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

EFS
NM_005864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.805

Publications

0 publications found

Variant links:

Genes affected

EFS (HGNC:16898): (embryonal Fyn-associated substrate) The protein encoded by this gene is a member of the CAS (CRK-associated substrate) family of adaptor proteins which typically serve as scaffolds for the assembly of larger signaling complexes. These complexes form at the cell surface where integrin binding leads to the subsequent phosphorylation of a CAS protein. Additional binding of SRC family kinases leads to CAS hyperphosphorylation and the creation of binding sites for CRK and other proteins that cause actin cytoskeleton reorganization. This gene plays a role in integrin-mediated cell attachment, spreading, and migration and also plays a role in both normal and malignant cellular transformation. This broadly expressed gene has been shown to play a role in neurite outgrowth and its expression in the thymus and lymphocytes is important for T cell maturation and the development of immunological self-tolerance. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

EFS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17194971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFS	NM_005864.4	MANE Select	c.1051A>G	p.Lys351Glu	missense	Exon 4 of 6	NP_005855.1	O43281-1
EFS	NM_032459.3		c.772A>G	p.Lys258Glu	missense	Exon 3 of 5	NP_115835.1	O43281-2
EFS	NM_001385607.1		c.772A>G	p.Lys258Glu	missense	Exon 3 of 4	NP_001372536.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFS	ENST00000216733.8	TSL:1 MANE Select	c.1051A>G	p.Lys351Glu	missense	Exon 4 of 6	ENSP00000216733.3	O43281-1
EFS	ENST00000351354.3	TSL:1	c.772A>G	p.Lys258Glu	missense	Exon 3 of 5	ENSP00000340607.3	O43281-2
EFS	ENST00000923553.1		c.1051A>G	p.Lys351Glu	missense	Exon 4 of 5	ENSP00000593612.1

Frequencies

GnomAD3 genomes

AF:

0.0000470

AC:

AN:

127544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000776

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000668

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000347

AC:

AN:

230742

AF XY:

0.0000475

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000483

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000406

AC:

AN:

1207994

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

598986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26142

American (AMR)

AF:

0.0000287

AC:

AN:

34814

Ashkenazi Jewish (ASJ)

AF:

0.0000587

AC:

AN:

17022

East Asian (EAS)

AF:

0.00

AC:

AN:

19056

South Asian (SAS)

AF:

0.0000518

AC:

AN:

77288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32170

Middle Eastern (MID)

AF:

0.000442

AC:

AN:

4522

European-Non Finnish (NFE)

AF:

0.0000357

AC:

AN:

952462

Other (OTH)

AF:

0.000157

AC:

AN:

44518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000470

AC:

AN:

127544

Hom.:

Cov.:

AF XY:

0.0000487

AC XY:

AN XY:

61662

show subpopulations

African (AFR)

AF:

0.0000291

AC:

AN:

34394

American (AMR)

AF:

0.0000776

AC:

AN:

12886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3186

East Asian (EAS)

AF:

0.00

AC:

AN:

3596

South Asian (SAS)

AF:

0.00

AC:

AN:

3428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0000668

AC:

AN:

59872

Other (OTH)

AF:

0.00

AC:

AN:

1752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000333

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.84

M_CAP

Benign

0.023

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

0.81

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.15

REVEL

Benign

0.20

Sift

Uncertain

0.025

Sift4G

Benign

0.78

Polyphen

0.88

Vest4

0.41

MutPred

0.36

Loss of ubiquitination at K351 (P = 0.0023)

MVP

0.70

MPC

0.17

ClinPred

0.23

GERP RS

4.7

Varity_R

0.15

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over