chr8-131940540-C-T

Variant names:

• chr8-131940540-C-T
• rs369257948
• ENST00000519656.1:c.-57C>T

Variant summary

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

The NM_001323553.2(EFR3A):​c.-126C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,608,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: EFR3A NM_001323553.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323553.2. 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>T	p.Arg18Cys	missense	Exon 2 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323553.2		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	NP_001310482.1	Q14156-2
	EFR3A	NM_001323554.2		c.-57C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	NP_001310483.1	Q14156-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3A	ENST00000519656.1	TSL:1	c.-57C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000254624.10	TSL:1 MANE Select	c.52C>T	p.Arg18Cys	missense	Exon 2 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.-57C>T		5_prime_UTR	Exon 2 of 23	ENSP00000428086.1	Q14156-2

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 151096 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: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 243502 AF XY: 0.00000758

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1457026 Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 724426

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.0000452 AC: 2 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39520

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52934

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5754

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1109730

Other (OTH) AF: 0.00 AC: 0 AN: 60186

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 151096 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73664

African (AFR) AF: 0.00 AC: 0 AN: 41042

American (AMR) AF: 0.00 AC: 0 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10332

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

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67880

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000602 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000331 AC: 4

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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MVP		0.53
MPC		0.44
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.56
gMVP		0.49
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV54453287;