Variant 17-62407159-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000305286.8(EFCAB3):c.814C>A(p.Pro272Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,603,960 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P272A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 2 hom. )

Consequence

EFCAB3
ENST00000305286.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29437608).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.814C>A	p.Pro272Thr	missense_variant	8/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.970C>A	p.Pro324Thr	missense_variant	10/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.880C>A	p.Pro294Thr	missense_variant	8/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.814C>A	p.Pro272Thr	missense_variant	8/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.814C>A	p.Pro272Thr	missense_variant	8/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.970C>A	p.Pro324Thr	missense_variant	10/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.1199C>A		non_coding_transcript_exon_variant	12/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000157

AC:

AN:

242598

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

130922

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000927

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000224

Gnomad SAS exome

AF:

0.000816

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.0000964

AC:

140

AN:

1451812

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

103

AN XY:

721824

show subpopulations

Gnomad4 AFR exome

AF:

0.000456

Gnomad4 AMR exome

AF:

0.0000941

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000416

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000198

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

Jul 13, 2021

The c.970C>A (p.P324T) alteration is located in exon 10 (coding exon 10) of the EFCAB3 gene. This alteration results from a C to A substitution at nucleotide position 970, causing the proline (P) at amino acid position 324 to be replaced by a threonine (T). 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

0.27

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

0.053

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.53

Sift

Benign

0.069

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.51

MutPred

0.53

.;Loss of helix (P = 0.0104);

MVP

0.95

MPC

0.68

ClinPred

0.12

GERP RS

5.9

Varity_R

0.17

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

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