Variant chr17-62406536-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 NM_173503.4(EFCAB3):c.545C>T(p.Thr182Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EFCAB3
NM_173503.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0650

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=0.13387728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.545C>T	p.Thr182Ile	missense_variant	7/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.701C>T	p.Thr234Ile	missense_variant	9/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.611C>T	p.Thr204Ile	missense_variant	7/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.545C>T	p.Thr182Ile	missense_variant	7/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.545C>T	p.Thr182Ile	missense_variant	7/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.701C>T	p.Thr234Ile	missense_variant	9/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.930C>T		non_coding_transcript_exon_variant	11/14	5
EFCAB3	ENST00000520404.5 linkuse as main transcript			downstream_gene_variant		5		ENSP00000429124

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727188

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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 17, 2021

The c.701C>T (p.T234I) alteration is located in exon 9 (coding exon 9) of the EFCAB3 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the threonine (T) at amino acid position 234 to be replaced by an isoleucine (I). 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

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.8

DANN

Benign

0.93

DEOGEN2

Benign

0.0040

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.040

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.038

D;D

Polyphen

0.089

.;B

Vest4

0.34

MutPred

0.44

.;Gain of helix (P = 0.0164);

MVP

0.69

MPC

0.18

ClinPred

0.051

GERP RS

1.5

Varity_R

0.032

gMVP

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over