GeneBe

rs780224177

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005864.4(EFS):​c.1291G>T​(p.Gly431*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

EFS
NM_005864.4 stop_gained

Scores

2
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EFSNM_005864.4 linkc.1291G>T p.Gly431* stop_gained Exon 6 of 6 ENST00000216733.8 NP_005855.1 O43281-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EFSENST00000216733.8 linkc.1291G>T p.Gly431* stop_gained Exon 6 of 6 1 NM_005864.4 ENSP00000216733.3 O43281-1
EFSENST00000351354.3 linkc.1012G>T p.Gly338* stop_gained Exon 5 of 5 1 ENSP00000340607.3 O43281-2
EFSENST00000429593.6 linkc.784G>T p.Gly262* stop_gained Exon 6 of 6 2 ENSP00000416684.2 O43281-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1406676
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
690836
African (AFR)
AF:
0.00
AC:
0
AN:
32516
American (AMR)
AF:
0.00
AC:
0
AN:
41874
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23172
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38644
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78336
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51722
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5446
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1077106
Other (OTH)
AF:
0.00
AC:
0
AN:
57860
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
37
DANN
Uncertain
0.99
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.93
D
PhyloP100
1.2
Vest4
0.70
GERP RS
3.8
Mutation Taster
=22/178
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.21
Position offset: 39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs780224177; hg19: chr14-23826830; API