Variant chr17-62416018-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 NM_173503.4(EFCAB3):c.1006G>A(p.Asp336Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,612,442 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 1 hom. )

Consequence

EFCAB3
NM_173503.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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=0.20613465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	10/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.1162G>A	p.Asp388Asn	missense_variant	12/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.1072G>A	p.Asp358Asn	missense_variant	10/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	10/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	10/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.1162G>A	p.Asp388Asn	missense_variant	12/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.1391G>A		non_coding_transcript_exon_variant	14/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249716

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

135034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000988

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1460260

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

726358

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:

0.000151

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Aug 14, 2023

The c.1162G>A (p.D388N) alteration is located in exon 12 (coding exon 12) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 1162, causing the aspartic acid (D) at amino acid position 388 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

0.72

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.60

.;P

Vest4

0.23

MutPred

0.21

.;Gain of MoRF binding (P = 0.0379);

MVP

0.81

MPC

0.51

ClinPred

0.15

GERP RS

4.5

Varity_R

0.11

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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