chr8-131940520-C-T

Variant names:

• chr8-131940520-C-T
• rs747685013
• NM_015137.6:c.32C>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.32C>T​(p.Ala11Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000591 in 1,454,516 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: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000059 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFR3A NM_015137.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• 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=0.37961072).

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.32C>T	p.Ala11Val	missense	Exon 2 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.32C>T	p.Ala11Val	missense	Exon 2 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.-146C>T		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.32C>T	p.Ala11Val	missense	Exon 2 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.-77C>T		5_prime_UTR	Exon 2 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.113C>T	p.Ala38Val	missense	Exon 2 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150832 Hom.: 0 Cov.: 31

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240276 AF XY: 0.00000768

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: 0.0000276

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000591 AC: 86 AN: 1454516 Hom.: 0 Cov.: 33 AF XY: 0.0000456 AC XY: 33 AN XY: 723034

African (AFR) AF: 0.0000300 AC: 1 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 44044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 84886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000767 AC: 85 AN: 1108622

Other (OTH) AF: 0.00 AC: 0 AN: 60072

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73504

African (AFR) AF: 0.00 AC: 0 AN: 40972

American (AMR) AF: 0.00 AC: 0 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67802

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000371 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.37
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.054	T
Polyphen		0.81	P
Vest4		0.58
MVP		0.55
MPC		0.18
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.43
Mutation Taster		=260/40	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: rs747685013; hg19: chr8-132952767;