Variant chr17-62387341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173503.4(EFCAB3):c.76G>A(p.Asp26Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,609,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

EFCAB3
NM_173503.4 missense, splice_region

Scores

Splicing: ADA: 0.005249

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.425

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:

EFCAB3 (HGNC:):

EFCAB3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015811741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_173503.4 linkuse as main transcript	c.76G>A	p.Asp26Asn	missense_variant, splice_region_variant	3/10	ENST00000305286.8	NP_775774.1	Q8N7B9-1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.232G>A	p.Asp78Asn	missense_variant, splice_region_variant	5/12		NP_001138405.1	Q8N7B9-2
EFCAB3	XM_011524381.3 linkuse as main transcript	c.142G>A	p.Asp48Asn	missense_variant, splice_region_variant	3/10		XP_011522683.2	Q8N7B9
EFCAB3	XM_011524380.2 linkuse as main transcript	c.76G>A	p.Asp26Asn	missense_variant, splice_region_variant	3/10		XP_011522682.1	Q8N7B9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.76G>A	p.Asp26Asn	missense_variant, splice_region_variant	3/10	1	NM_173503.4	ENSP00000302649.3		Q8N7B9-1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000487

AC:

122

AN:

250280

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000282

Gnomad NFE exome

AF:

0.000785

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000494

AC:

720

AN:

1456840

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

390

AN XY:

724904

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000492

Gnomad4 NFE exome

AF:

0.000559

Gnomad4 OTH exome

AF:

0.000449

GnomAD4 genome

AF:

0.000460

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000841

Hom.:

Bravo

AF:

0.000393

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000519

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000415

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

Oct 18, 2021

The c.232G>A (p.D78N) alteration is located in exon 5 (coding exon 5) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 232, causing the aspartic acid (D) at amino acid position 78 to be replaced by an asparagine (N). 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

0.086

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

.;T;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.92

T;T;T;T

Polyphen

0.28, 0.26

.;B;B;.

Vest4

0.091

MVP

0.68

MPC

0.15

ClinPred

0.032

GERP RS

2.4

Varity_R

0.038

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0052

dbscSNV1_RF

Benign

0.064

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