14-89932616-C-G

Variant names:

• chr14-89932616-C-G
• rs144958103
• NM_145231.4:c.229G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145231.4(EFCAB11):​c.229G>C​(p.Glu77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E77K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB11 NM_145231.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14772907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB11	NM_145231.4	c.229G>C	p.Glu77Gln	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.229G>C	p.Glu77Gln	missense_variant	Exon 4 of 6	2	NM_145231.4	ENSP00000326267.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;.;.;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.066	N
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.079	T;T;D;T;D
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.57	P;P;.;.;B
Vest4		0.082
MutPred		0.53		Gain of MoRF binding (P = 0.0303);.;.;Gain of MoRF binding (P = 0.0303);.;
MVP		0.61
MPC		0.064
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.072
gMVP		0.40

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

Other links and lift over

dbSNP: rs144958103; hg19: chr14-90398960;