rs369257948

Variant names:

• chr8-131940540-C-G
• rs369257948
• NM_015137.6:c.52C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-131940540-C-G
• chr8-131940540-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015137.6(EFR3A):​c.52C>G​(p.Arg18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R18H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EFR3A NM_015137.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

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.52C>G	p.Arg18Gly	missense	Exon 2 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.52C>G	p.Arg18Gly	missense	Exon 2 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.-126C>G		5_prime_UTR	Exon 2 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.52C>G	p.Arg18Gly	missense	Exon 2 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.-57C>G		5_prime_UTR	Exon 2 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.133C>G	p.Arg45Gly	missense	Exon 2 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.2
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.66		Loss of stability (P = 0.0152)
MVP		0.51
MPC		0.42
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.69
gMVP		0.51
Mutation Taster		=12/88	disease causing

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: rs369257948; hg19: chr8-132952787;