dbSNP rs753502762: EFS:p.Arg343Leu (chr14-23359450-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005864.4(EFS):c.1028G>T(p.Arg343Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000247 in 404,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R343C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

EFS
NM_005864.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0130

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07583907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFS	NM_005864.4 link	c.1028G>T	p.Arg343Leu	missense_variant	Exon 4 of 6	ENST00000216733.8	NP_005855.1	O43281-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EFS	ENST00000216733.8 link	c.1028G>T	p.Arg343Leu	missense_variant	Exon 4 of 6	1	NM_005864.4	ENSP00000216733.3	O43281-1
EFS	ENST00000351354.3 link	c.749G>T	p.Arg250Leu	missense_variant	Exon 3 of 5	1		ENSP00000340607.3	O43281-2
EFS	ENST00000429593.6 link	c.521G>T	p.Arg174Leu	missense_variant	Exon 4 of 6	2		ENSP00000416684.2	O43281-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000247

AC:

AN:

404266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

217592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000373

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.068

T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.85

D;T;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.92

N;N;N

REVEL

Benign

0.076

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.053

B;.;P

Vest4

0.15

MutPred

0.35

Loss of methylation at R343 (P = 0.0388);.;.;

MVP

0.65

MPC

0.22

ClinPred

0.38

GERP RS

3.8

Varity_R

0.062

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over