14-23357501-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005864.4(EFS):c.1411G>A(p.Val471Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000632 in 1,613,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000061 ( 1 hom. )
Consequence
EFS
NM_005864.4 missense
NM_005864.4 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 5.78
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]
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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=0.21529478).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFS | NM_005864.4 | c.1411G>A | p.Val471Met | missense_variant | 6/6 | ENST00000216733.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFS | ENST00000216733.8 | c.1411G>A | p.Val471Met | missense_variant | 6/6 | 1 | NM_005864.4 | P1 | |
EFS | ENST00000351354.3 | c.1132G>A | p.Val378Met | missense_variant | 5/5 | 1 | |||
EFS | ENST00000429593.6 | c.904G>A | p.Val302Met | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250656Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135736
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461600Hom.: 1 Cov.: 30 AF XY: 0.0000674 AC XY: 49AN XY: 727100
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74376
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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 | Feb 16, 2023 | The c.1411G>A (p.V471M) alteration is located in exon 6 (coding exon 6) of the EFS gene. This alteration results from a G to A substitution at nucleotide position 1411, causing the valine (V) at amino acid position 471 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of sheet (P = 0.0817);.;.;
MVP
MPC
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at