Variant 2-25093095-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_014971.2(EFR3B):c.177G>C(p.Glu59Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,551,748 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 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

EFR3B
NM_014971.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

EFR3B (HGNC:29155): (EFR3 homolog B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFR3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, EFR3B

BP4

Computational evidence support a benign effect (MetaRNN=0.1898396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3B	NM_014971.2 linkuse as main transcript	c.177G>C	p.Glu59Asp	missense_variant	3/23	ENST00000403714.8
EFR3B	NM_001319099.2 linkuse as main transcript	c.72G>C	p.Glu24Asp	missense_variant	3/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3B	ENST00000403714.8 linkuse as main transcript	c.177G>C	p.Glu59Asp	missense_variant	3/23	5	NM_014971.2	P1	Q9Y2G0-1
EFR3B	ENST00000402191.5 linkuse as main transcript	c.72G>C	p.Glu24Asp	missense_variant	3/23	5
EFR3B	ENST00000401432.7 linkuse as main transcript	c.177G>C	p.Glu59Asp	missense_variant	3/19	2			Q9Y2G0-3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000196

AC:

AN:

158272

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

83386

show subpopulations

Gnomad AFR exome

AF:

0.000121

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000434

AC:

607

AN:

1399582

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

282

AN XY:

690230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000949

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.000535

Gnomad4 OTH exome

AF:

0.000292

GnomAD4 genome

AF:

0.000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000455

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000194

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.177G>C (p.E59D) alteration is located in exon 3 (coding exon 3) of the EFR3B gene. This alteration results from a G to C substitution at nucleotide position 177, causing the glutamic acid (E) at amino acid position 59 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.044

B;D;.

Vest4

0.42

MutPred

0.23

Loss of phosphorylation at Y56 (P = 0.103);Loss of phosphorylation at Y56 (P = 0.103);.;

MVP

0.11

ClinPred

0.10

GERP RS

3.8

Varity_R

0.30

gMVP

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over