chr17-47335311-A-T

Position:

• chr17-47335311-A-T

Variant summary

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

The NM_152347.5(EFCAB13):​c.146A>T​(p.Glu49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.587

Genes affected

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

ENSG00000259753 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.146A>T	p.Glu49Val	missense_variant	5/25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.146A>T	p.Glu49Val	missense_variant	5/25	1	NM_152347.5	ENSP00000332111.2
ENSG00000259753	ENST00000560629.1	n.*135A>T		non_coding_transcript_exon_variant	16/18	2		ENSP00000456711.2
ENSG00000259753	ENST00000560629.1	n.*135A>T		3_prime_UTR_variant	16/18	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.146A>T (p.E49V) alteration is located in exon 5 (coding exon 2) of the EFCAB13 gene. This alteration results from a A to T substitution at nucleotide position 146, causing the glutamic acid (E) at amino acid position 49 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.00037	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.24	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.88	N;D;N
REVEL	Benign	0.080
Sift	Uncertain	0.020	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.0	B;.;.
Vest4		0.10
MVP		0.014
MPC		0.16
ClinPred		0.089	T
GERP RS		-2.4
Varity_R		0.080
gMVP		0.032

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -2
DS_DL_spliceai		0.22		Position offset: 45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs770550643; hg19: chr17-45412677;