chr14-89932616-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145231.4(EFCAB11):​c.229G>T​(p.Glu77*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EFCAB11 NM_145231.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145231.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB11	NM_145231.4	MANE Select	c.229G>T	p.Glu77*	stop_gained	Exon 4 of 6	NP_660274.1	Q9BUY7-1
	EFCAB11	NM_001284266.2		c.229G>T	p.Glu77*	stop_gained	Exon 4 of 6	NP_001271195.1	Q9BUY7-5
	EFCAB11	NM_001284269.2		c.157G>T	p.Glu53*	stop_gained	Exon 4 of 6	NP_001271198.1	Q9BUY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB11	ENST00000316738.12	TSL:2 MANE Select	c.229G>T	p.Glu77*	stop_gained	Exon 4 of 6	ENSP00000326267.7	Q9BUY7-1
	EFCAB11	ENST00000555872.5	TSL:1	c.157G>T	p.Glu53*	stop_gained	Exon 4 of 6	ENSP00000452320.1	Q9BUY7-2
	EFCAB11	ENST00000556005.1	TSL:1	c.157G>T	p.Glu53*	stop_gained	Exon 4 of 6	ENSP00000452143.1	Q9BUY7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460992 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726852

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111522

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.080	N
PhyloP100		0.64
Vest4		0.37
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=54/146	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs144958103; hg19: chr14-90398960;