8-131953850-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015137.6(EFR3A):c.521G>A(p.Gly174Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000449 in 1,560,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

EFR3A
NM_015137.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90

Variant links:

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]

EFR3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3A	NM_015137.6 linkuse as main transcript	c.521G>A	p.Gly174Asp	missense_variant	6/23	ENST00000254624.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3A	ENST00000254624.10 linkuse as main transcript	c.521G>A	p.Gly174Asp	missense_variant	6/23	1	NM_015137.6	P3	Q14156-1
EFR3A	ENST00000519656.1 linkuse as main transcript	c.413G>A	p.Gly138Asp	missense_variant	6/23	1		A1	Q14156-2
EFR3A	ENST00000637848.1 linkuse as main transcript	c.602G>A	p.Gly201Asp	missense_variant	6/23	5
EFR3A	ENST00000522709.5 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

150026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183566

Hom.:

AF XY:

0.00

AC XY:

AN XY:

96922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1410694

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697336

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:

0.00000554

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000667

AC:

AN:

150026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73050

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 03, 2022

The c.521G>A (p.G174D) alteration is located in exon 6 (coding exon 6) of the EFR3A gene. This alteration results from a G to A substitution at nucleotide position 521, causing the glycine (G) at amino acid position 174 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Uncertain

-0.011

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-6.1

D;.;D

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.0020

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.98

MutPred

0.64

Gain of relative solvent accessibility (P = 0.0479);.;.;

MVP

0.77

MPC

0.43

ClinPred

0.99

GERP RS

5.6

Varity_R

0.88

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over