17-62416012-G-A

Position:

• chr17-62416012-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000305286.8(EFCAB3):​c.1000G>A​(p.Ala334Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB3 ENST00000305286.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40520197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_173503.4	c.1000G>A	p.Ala334Thr	missense_variant	10/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2	c.1156G>A	p.Ala386Thr	missense_variant	12/12		NP_001138405.1
EFCAB3	XM_011524381.3	c.1066G>A	p.Ala356Thr	missense_variant	10/10		XP_011522683.2
EFCAB3	XM_011524380.2	c.1000G>A	p.Ala334Thr	missense_variant	10/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8	c.1000G>A	p.Ala334Thr	missense_variant	10/10	1	NM_173503.4	ENSP00000302649	P1
EFCAB3	ENST00000450662.7	c.1156G>A	p.Ala386Thr	missense_variant	12/12	5		ENSP00000403932
EFCAB3	ENST00000636041.1	n.1385G>A		non_coding_transcript_exon_variant	14/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 28, 2023

The c.1156G>A (p.A386T) alteration is located in exon 12 (coding exon 12) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 1156, causing the alanine (A) at amino acid position 386 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0089	.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	0.93	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.47
MutPred		0.29		.;Loss of helix (P = 0.0558);
MVP		0.89
MPC		0.57
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.10
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2070544224; hg19: chr17-60493373;