Variant chr3-129418267-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207307.3(EFCAB12):c.668C>T(p.Ala223Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,610,462 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

EFCAB12
NM_207307.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.23

Variant links:

Genes affected

EFCAB12 (HGNC:28061): (EF-hand calcium binding domain 12) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009023905).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB12	NM_207307.3 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	3/9	ENST00000505956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EFCAB12	ENST00000505956.6 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	3/9	1	NM_207307.3	P1
EFCAB12	ENST00000503957.1 linkuse as main transcript	c.218C>T	p.Ala73Val	missense_variant	2/4	5
EFCAB12	ENST00000503498.1 linkuse as main transcript	n.399C>T		non_coding_transcript_exon_variant	2/7	2
EFCAB12	ENST00000514900.5 linkuse as main transcript	n.257C>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000110

AC:

AN:

246360

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

133620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.000531

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1458270

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

725278

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000770

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000550

Gnomad4 OTH exome

AF:

0.000648

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000104

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000992

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000110

EpiControl

AF:

0.0000597

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

Jul 20, 2021

The c.668C>T (p.A223V) alteration is located in exon 3 (coding exon 3) of the EFCAB12 gene. This alteration results from a C to T substitution at nucleotide position 668, causing the alanine (A) at amino acid position 223 to be replaced by a valine (V). 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

0.082

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.015

DANN

Benign

0.18

DEOGEN2

Benign

0.00071

T;T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.58

N;N;N

REVEL

Benign

0.029

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.99

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.047

MutPred

0.29

Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);.;

MVP

0.055

MPC

0.068

ClinPred

0.0084

GERP RS

-9.5

Varity_R

0.020

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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