Variant 17-62413831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000305286.8(EFCAB3):c.967G>A(p.Asp323Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,610,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

EFCAB3
ENST00000305286.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2154586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	9/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant	11/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.1033G>A	p.Asp345Asn	missense_variant	9/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	9/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	9/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant	11/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.1352G>A		non_coding_transcript_exon_variant	13/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248168

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458770

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725720

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Dec 18, 2023

The c.1123G>A (p.D375N) alteration is located in exon 11 (coding exon 11) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 1123, causing the aspartic acid (D) at amino acid position 375 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

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.0

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.15

Sift

Benign

0.086

T;T

Sift4G

Uncertain

0.013

D;D

Polyphen

0.019

.;B

Vest4

0.14

MutPred

0.31

.;Gain of MoRF binding (P = 0.0294);

MVP

0.75

MPC

0.36

ClinPred

0.20

GERP RS

4.9

Varity_R

0.054

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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