8-131953872-C-A

Variant names:

• chr8-131953872-C-A
• rs11984595
• NM_015137.6:c.543C>A

Variant summary

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

The NM_015137.6(EFR3A):​c.543C>A​(p.Asn181Lys) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N181N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFR3A NM_015137.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28384757).

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.543C>A	p.Asn181Lys	missense	Exon 6 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.543C>A	p.Asn181Lys	missense	Exon 6 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.435C>A	p.Asn145Lys	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.543C>A	p.Asn181Lys	missense	Exon 6 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.435C>A	p.Asn145Lys	missense	Exon 6 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.624C>A	p.Asn208Lys	missense	Exon 6 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 198144 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422558 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 704024

African (AFR) AF: 0.00 AC: 0 AN: 32648

American (AMR) AF: 0.00 AC: 0 AN: 39456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 38134

South Asian (SAS) AF: 0.00 AC: 0 AN: 81064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090080

Other (OTH) AF: 0.00 AC: 0 AN: 58888

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.43
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		0.86	P
Vest4		0.48
MutPred		0.38		Gain of MoRF binding (P = 0.0311)
MVP		0.27
MPC		0.20
ClinPred		0.98	D
GERP RS		-0.80
Varity_R		0.40
gMVP		0.56
Mutation Taster		=45/55	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: rs11984595; hg19: chr8-132966119;