17-47370454-A-T

Variant names:

• chr17-47370454-A-T
• NM_152347.5:c.823A>T

Variant summary

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

The NM_152347.5(EFCAB13):​c.823A>T​(p.Ile275Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

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=0.1158739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.823A>T	p.Ile275Phe	missense_variant	Exon 11 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.823A>T	p.Ile275Phe	missense_variant	Exon 11 of 25	1	NM_152347.5	ENSP00000332111.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449002 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 721766

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0020	.;T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.043
Sift	Uncertain	0.013	.;D;D
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		0.19	.;B;.
Vest4		0.29, 0.31
MutPred		0.29		.;Gain of catalytic residue at M272 (P = 0.1133);.;
MVP		0.055
MPC		0.75
ClinPred		0.24	T
GERP RS		0.079
Varity_R		0.11
gMVP		0.23

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: chr17-45447820;