Genetic Variant EFR3B:p.Val313Met (chr2-25131455-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014971.2(EFR3B):c.937G>A(p.Val313Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

EFR3B
NM_014971.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.77

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFR3B	NM_014971.2 link	c.937G>A	p.Val313Met	missense_variant	Exon 9 of 23	ENST00000403714.8	NP_055786.1	Q9Y2G0-1B3KT90
EFR3B	NM_001319099.2 link	c.832G>A	p.Val278Met	missense_variant	Exon 9 of 23		NP_001306028.1	E7ESK9B3KT90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFR3B	ENST00000403714.8 link	c.937G>A	p.Val313Met	missense_variant	Exon 9 of 23	5	NM_014971.2	ENSP00000384081.3		Q9Y2G0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000662

AC:

AN:

151074

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000930

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398318

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.937G>A (p.V313M) alteration is located in exon 9 (coding exon 9) of the EFR3B gene. This alteration results from a G to A substitution at nucleotide position 937, causing the valine (V) at amino acid position 313 to be replaced by a methionine (M). 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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.57

D;D;D;D;D

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.3

M;M;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.040

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

0.98

D;P;.;.;.

Vest4

0.65

MutPred

0.39

Loss of methylation at R309 (P = 0.2165);Loss of methylation at R309 (P = 0.2165);.;.;.;

MVP

0.12

ClinPred

0.81

GERP RS

4.5

Varity_R

0.20

gMVP

0.81

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