Variant 17-47344264-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000331493.7(EFCAB13):c.406C>T(p.Pro136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,354 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

EFCAB13
ENST00000331493.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.359

Variant links:

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13 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=0.102995366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB13	NM_152347.5 linkuse as main transcript	c.406C>T	p.Pro136Ser	missense_variant	7/25	ENST00000331493.7	NP_689560.3
EFCAB13	NM_001195192.2 linkuse as main transcript	c.406C>T	p.Pro136Ser	missense_variant	7/22		NP_001182121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7 linkuse as main transcript	c.406C>T	p.Pro136Ser	missense_variant	7/25	1	NM_152347.5	ENSP00000332111	A2	Q8IY85-1
EFCAB13	ENST00000517484.5 linkuse as main transcript	c.406C>T	p.Pro136Ser	missense_variant	7/22	2		ENSP00000430048	P2	Q8IY85-2
EFCAB13	ENST00000517310.5 linkuse as main transcript	c.-39C>T		5_prime_UTR_variant	8/11	2		ENSP00000466136
EFCAB13	ENST00000520776.5 linkuse as main transcript	n.540C>T		non_coding_transcript_exon_variant	5/14	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250530

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000298

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:

0.000164

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460228

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726360

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Sep 01, 2021

The c.406C>T (p.P136S) alteration is located in exon 7 (coding exon 4) of the EFCAB13 gene. This alteration results from a C to T substitution at nucleotide position 406, causing the proline (P) at amino acid position 136 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.059

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.28

T;T

Polyphen

0.87

P;.

Vest4

0.26

MVP

0.076

MPC

0.24

ClinPred

0.12

GERP RS

-0.0052

Varity_R

0.052

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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