8-131946605-C-G

Variant names:

• chr8-131946605-C-G
• rs747042864
• NM_015137.6:c.338C>G

Variant summary

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

The NM_015137.6(EFR3A):​c.338C>G​(p.Pro113Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,192 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P113S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EFR3A NM_015137.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015137.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3A	NM_015137.6	MANE Select	c.338C>G	p.Pro113Arg	missense	Exon 4 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.338C>G	p.Pro113Arg	missense	Exon 4 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.230C>G	p.Pro77Arg	missense	Exon 4 of 23	NP_001310482.1	Q14156-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3A	ENST00000254624.10	TSL:1 MANE Select	c.338C>G	p.Pro113Arg	missense	Exon 4 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.230C>G	p.Pro77Arg	missense	Exon 4 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.419C>G	p.Pro140Arg	missense	Exon 4 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451192 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721382

African (AFR) AF: 0.00 AC: 0 AN: 32920

American (AMR) AF: 0.00 AC: 0 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39200

South Asian (SAS) AF: 0.00 AC: 0 AN: 84216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107086

Other (OTH) AF: 0.00 AC: 0 AN: 59900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.84	P
Vest4		0.89
MutPred		0.39		Loss of ubiquitination at K114 (P = 0.0496)
MVP		0.50
MPC		0.28
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		0.83
Mutation Taster		=15/85	disease causing

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

Other links and lift over

dbSNP: rs747042864; hg19: chr8-132958852;