17-47335341-C-T

Variant names:

• chr17-47335341-C-T
• NM_152347.5:c.176C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152347.5(EFCAB13):​c.176C>T​(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,082 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: 7.0e-7 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

Genes affected

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

ENSG00000259753 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045213223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.176C>T	p.Pro59Leu	missense_variant	Exon 5 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.176C>T	p.Pro59Leu	missense_variant	Exon 5 of 25	1	NM_152347.5	ENSP00000332111.2
ENSG00000259753	ENST00000560629.1	n.*165C>T		non_coding_transcript_exon_variant	Exon 16 of 18	2		ENSP00000456711.2
ENSG00000259753	ENST00000560629.1	n.*165C>T		3_prime_UTR_variant	Exon 16 of 18	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434082 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712994

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: 9.05e-7

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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.99	T;T
Polyphen		0.015	B;.
Vest4		0.086
MutPred		0.30		Loss of ubiquitination at K62 (P = 0.0424);Loss of ubiquitination at K62 (P = 0.0424);
MVP		0.061
MPC		0.15
ClinPred		0.057	T
GERP RS		0.37
Varity_R		0.10
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr17-45412707;