chr17-47345080-C-T

Variant names:

• chr17-47345080-C-T
• rs144149515
• NM_152347.5:c.499C>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.499C>T​(p.His167Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,352 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: -2.73

Genes affected

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

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=0.027938068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.499C>T	p.His167Tyr	missense_variant	Exon 8 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.499C>T	p.His167Tyr	missense_variant	Exon 8 of 25	1	NM_152347.5	ENSP00000332111.2
EFCAB13	ENST00000517484.5	c.499C>T	p.His167Tyr	missense_variant	Exon 8 of 22	2		ENSP00000430048.1
EFCAB13	ENST00000517310.5	c.55C>T	p.His19Tyr	missense_variant	Exon 9 of 11	2		ENSP00000466136.1
EFCAB13	ENST00000520776.5	n.633C>T		non_coding_transcript_exon_variant	Exon 6 of 14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450352 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721378

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

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	0.055
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0060
DANN	Benign	0.48
DEOGEN2	Benign	0.00047	.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00039	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	.;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.24	.;N;N
REVEL	Benign	0.032
Sift	Benign	0.54	.;T;T
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.11, 0.12
MutPred		0.29		.;Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);
MVP		0.014
MPC		0.16
ClinPred		0.042	T
GERP RS		-7.0
Varity_R		0.031
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs144149515; hg19: chr17-45422446;