8-131953872-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_015137.6(EFR3A):​c.543C>T​(p.Asn181Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,572,810 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00020 (4 hom.)
• Consequence: EFR3A NM_015137.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 8-131953872-C-T is Benign according to our data. Variant chr8-131953872-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058019.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.432 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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>T	p.Asn181Asn	synonymous	Exon 6 of 23	NP_055952.2	Q14156-1
	EFR3A	NM_001323558.2		c.543C>T	p.Asn181Asn	synonymous	Exon 6 of 24	NP_001310487.1
	EFR3A	NM_001323553.2		c.435C>T	p.Asn145Asn	synonymous	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>T	p.Asn181Asn	synonymous	Exon 6 of 23	ENSP00000254624.5	Q14156-1
	EFR3A	ENST00000519656.1	TSL:1	c.435C>T	p.Asn145Asn	synonymous	Exon 6 of 23	ENSP00000428086.1	Q14156-2
	EFR3A	ENST00000637848.1	TSL:5	c.624C>T	p.Asn208Asn	synonymous	Exon 6 of 23	ENSP00000490312.1	A0A1B0GUZ7

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 359 AN: 150160 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00247

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: 0.00194

GnomAD2 exomes AF: 0.000671 AC: 133 AN: 198144 AF XY: 0.000447

Gnomad AFR exome AF: 0.00846

Gnomad AMR exome AF: 0.000800

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: 0.000576

GnomAD4 exome AF: 0.000200 AC: 284 AN: 1422554 Hom.: 4 Cov.: 33 AF XY: 0.000155 AC XY: 109 AN XY: 704024

African (AFR) AF: 0.00659 AC: 215 AN: 32644

American (AMR) AF: 0.000735 AC: 29 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: 0.0000123 AC: 1 AN: 81064

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

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 0.00000367 AC: 4 AN: 1090080

Other (OTH) AF: 0.000577 AC: 34 AN: 58888

GnomAD4 genome AF: 0.00239 AC: 359 AN: 150256 Hom.: 0 Cov.: 31 AF XY: 0.00232 AC XY: 170 AN XY: 73190

African (AFR) AF: 0.00778 AC: 318 AN: 40882

American (AMR) AF: 0.00247 AC: 37 AN: 14990

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67720

Other (OTH) AF: 0.00192 AC: 4 AN: 2082

Alfa AF: 0.000944 Hom.: 0

Bravo AF: 0.00311

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EFR3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		0.43

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;