rs1818836322

Variant names:

• chr8-131953882-C-T
• rs1818836322
• NM_015137.6:c.553C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015137.6(EFR3A):​c.553C>T​(p.Arg185Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,642 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: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EFR3A NM_015137.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36628348).

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.553C>T	p.Arg185Trp	missense	Exon 6 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.553C>T	p.Arg185Trp	missense	Exon 6 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.445C>T	p.Arg149Trp	missense	Exon 6 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.553C>T	p.Arg185Trp	missense	Exon 6 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.445C>T	p.Arg149Trp	missense	Exon 6 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.634C>T	p.Arg212Trp	missense	Exon 6 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424642 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 705162

African (AFR) AF: 0.0000306 AC: 1 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 39758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 38250

South Asian (SAS) AF: 0.00 AC: 0 AN: 81348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091182

Other (OTH) AF: 0.00 AC: 0 AN: 58982

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.025	D
Polyphen		0.90	P
Vest4		0.53
MutPred		0.43		Loss of MoRF binding (P = 0.0582)
MVP		0.65
MPC		0.25
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.20
gMVP		0.54
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1818836322; hg19: chr8-132966129; COSMIC: COSV106378702; COSMIC: COSV106378702;