chr8-131950039-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015137.6(EFR3A):c.437G>A(p.Arg146Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,608,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
EFR3A
NM_015137.6 missense
NM_015137.6 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.64
Genes affected
EFR3A (HGNC:28970): (EFR3 homolog A) The protein encoded by this gene is part of a complex that plays a role in maintaining an active pool of phosphatidylinositol 4-kinase (PI4K) at the plasma membrane. This protein is thought to be a peripheral membrane protein that associates with the plasma membrane through palmitoylation. Studies indicate that this gene product plays a role in controlling G protein-coupled receptor (GPCR) activity by affecting receptor phosphorylation. Whole exome sequencing studies have implicated mutations in this gene with autism spectrum disorders. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2985242).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFR3A | NM_015137.6 | c.437G>A | p.Arg146Gln | missense_variant | 5/23 | ENST00000254624.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFR3A | ENST00000254624.10 | c.437G>A | p.Arg146Gln | missense_variant | 5/23 | 1 | NM_015137.6 | P3 | |
EFR3A | ENST00000519656.1 | c.329G>A | p.Arg110Gln | missense_variant | 5/23 | 1 | A1 | ||
EFR3A | ENST00000637848.1 | c.518G>A | p.Arg173Gln | missense_variant | 5/23 | 5 | |||
EFR3A | ENST00000522709.5 | c.329G>A | p.Arg110Gln | missense_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456116Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723988
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74206
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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 | Aug 28, 2023 | The c.437G>A (p.R146Q) alteration is located in exon 5 (coding exon 5) of the EFR3A gene. This alteration results from a G to A substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;.;T
Polyphen
P;.;.;.
Vest4
MutPred
Loss of phosphorylation at S148 (P = 0.1849);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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