17-62391899-G-A

Position:

• chr17-62391899-G-A

Variant summary

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

The NM_173503.4(EFCAB3):​c.229G>A​(p.Ala77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: EFCAB3 NM_173503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

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=0.30542982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_173503.4	c.229G>A	p.Ala77Thr	missense_variant	4/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2	c.385G>A	p.Ala129Thr	missense_variant	6/12		NP_001138405.1
EFCAB3	XM_011524381.3	c.295G>A	p.Ala99Thr	missense_variant	4/10		XP_011522683.2
EFCAB3	XM_011524380.2	c.229G>A	p.Ala77Thr	missense_variant	4/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8	c.229G>A	p.Ala77Thr	missense_variant	4/10	1	NM_173503.4	ENSP00000302649	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Mar 20, 2023

The c.385G>A (p.A129T) alteration is located in exon 6 (coding exon 6) of the EFCAB3 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the alanine (A) at amino acid position 129 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	0.13
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0038	.;T;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.76	.;N;.;.
MutationTaster	Benign	0.92	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.20	T;T;T;T
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.95, 1.0	.;P;D;.
Vest4		0.30
MutPred		0.40		.;Loss of ubiquitination at K78 (P = 0.1106);Loss of ubiquitination at K78 (P = 0.1106);Loss of ubiquitination at K78 (P = 0.1106);
MVP		0.80
MPC		0.36
ClinPred		0.66	D
GERP RS		4.2
Varity_R		0.058
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-60469260;