chr8-131953920-T-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_015137.6(EFR3A):c.591T>G(p.Ile197Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,572,242 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 9 hom. )
Consequence
EFR3A
NM_015137.6 missense
NM_015137.6 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 0.134
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009498179).
BP6
?
Variant 8-131953920-T-G is Benign according to our data. Variant chr8-131953920-T-G is described in ClinVar as [Benign]. Clinvar id is 3034454.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00117 (1665/1420118) while in subpopulation MID AF= 0.0273 (156/5712). AF 95% confidence interval is 0.0238. There are 9 homozygotes in gnomad4_exome. There are 863 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFR3A | NM_015137.6 | c.591T>G | p.Ile197Met | missense_variant | 6/23 | ENST00000254624.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFR3A | ENST00000254624.10 | c.591T>G | p.Ile197Met | missense_variant | 6/23 | 1 | NM_015137.6 | P3 | |
EFR3A | ENST00000519656.1 | c.483T>G | p.Ile161Met | missense_variant | 6/23 | 1 | A1 | ||
EFR3A | ENST00000637848.1 | c.672T>G | p.Ile224Met | missense_variant | 6/23 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00108 AC: 164AN: 152006Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00160 AC: 306AN: 190876Hom.: 0 AF XY: 0.00174 AC XY: 176AN XY: 101108
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GnomAD4 exome AF: 0.00117 AC: 1665AN: 1420118Hom.: 9 Cov.: 33 AF XY: 0.00123 AC XY: 863AN XY: 702448
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GnomAD4 genome ? AF: 0.00108 AC: 165AN: 152124Hom.: 0 Cov.: 31 AF XY: 0.00109 AC XY: 81AN XY: 74370
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
EFR3A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 02, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N
REVEL
Uncertain
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
T
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