Variant 17-62406491-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000305286.8(EFCAB3):c.500G>A(p.Arg167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,578,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

EFCAB3
ENST00000305286.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.843

Variant links:

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB3 links:

Genome browser will be placed here

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/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.500G>A	p.Arg167Lys	missense_variant	7/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.656G>A	p.Arg219Lys	missense_variant	9/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.566G>A	p.Arg189Lys	missense_variant	7/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.500G>A	p.Arg167Lys	missense_variant	7/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.500G>A	p.Arg167Lys	missense_variant	7/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.656G>A	p.Arg219Lys	missense_variant	9/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000520404.5 linkuse as main transcript	c.500G>A	p.Arg167Lys	missense_variant	7/7	5		ENSP00000429124
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.885G>A		non_coding_transcript_exon_variant	11/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

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

GnomAD3 exomes

AF:

0.0000431

AC:

AN:

231906

Hom.:

AF XY:

0.0000478

AC XY:

AN XY:

125554

show subpopulations

Gnomad AFR exome

AF:

0.000443

Gnomad AMR exome

AF:

0.0000344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000175

AC:

AN:

1426362

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

707708

show subpopulations

Gnomad4 AFR exome

AF:

0.000498

Gnomad4 AMR exome

AF:

0.0000259

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:

0.00000274

Gnomad4 OTH exome

AF:

0.0000511

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151648

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000323

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 03, 2021

The c.656G>A (p.R219K) alteration is located in exon 9 (coding exon 9) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 656, causing the arginine (R) at amino acid position 219 to be replaced by a lysine (K). 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

0.081

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.00079

.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.60

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0020, 0.0090

.;B;B

Vest4

0.21

MVP

0.60

MPC

0.15

ClinPred

0.016

GERP RS

3.2

Varity_R

0.043

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: -11

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