14-89932549-A-G

Variant names:

• chr14-89932549-A-G
• NM_145231.4:c.296T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145231.4(EFCAB11):​c.296T>C​(p.Ile99Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB11 NM_145231.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32

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]

ENSG00000259053 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB11	NM_145231.4	c.296T>C	p.Ile99Thr	missense_variant	Exon 4 of 6	ENST00000316738.12	NP_660274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB11	ENST00000316738.12	c.296T>C	p.Ile99Thr	missense_variant	Exon 4 of 6	2	NM_145231.4	ENSP00000326267.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.296T>C (p.I99T) alteration is located in exon 4 (coding exon 4) of the EFCAB11 gene. This alteration results from a T to C substitution at nucleotide position 296, causing the isoleucine (I) at amino acid position 99 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;.;.;.;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	2.0	M;.;.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.17	B;B;.;.;B
Vest4		0.74
MutPred		0.66		Gain of catalytic residue at A102 (P = 0.0014);.;.;Gain of catalytic residue at A102 (P = 0.0014);.;
MVP		0.79
MPC		0.11
ClinPred		0.89	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-90398893;