Variant 14-89954656-A-G 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_145231.4(EFCAB11):c.5T>C(p.Phe2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EFCAB11
NM_145231.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.946

Variant links:

Genes affected

EFCAB11 (HGNC:20357): (EF-hand calcium binding domain 11) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB11 links:

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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=0.11542964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EFCAB11	NM_145231.4 linkuse as main transcript	c.5T>C	p.Phe2Ser	missense_variant	1/6	ENST00000316738.12
EFCAB11	NM_001284266.2 linkuse as main transcript	c.5T>C	p.Phe2Ser	missense_variant	1/6
EFCAB11	NM_001284267.2 linkuse as main transcript	c.-70+77T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB11	ENST00000316738.12 linkuse as main transcript	c.5T>C	p.Phe2Ser	missense_variant	1/6	2	NM_145231.4	P1	Q9BUY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246600

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133898

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459772

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726254

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

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

May 24, 2023

The c.5T>C (p.F2S) alteration is located in exon 1 (coding exon 1) of the EFCAB11 gene. This alteration results from a T to C substitution at nucleotide position 5, causing the phenylalanine (F) at amino acid position 2 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

0.20

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0064

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.78

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.10

Sift

Benign

0.093

T;T

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.0010

B;.

Vest4

0.29

MutPred

0.24

Gain of phosphorylation at F2 (P = 0.0026);Gain of phosphorylation at F2 (P = 0.0026);

MVP

0.57

MPC

0.099

ClinPred

0.14

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.55

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