17-62383017-A-C

Position:

• chr17-62383017-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173503.4(EFCAB3):​c.38A>C​(p.Asn13Thr) 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. 14/21 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)
• Consequence: EFCAB3 NM_173503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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]

EFCAB3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15431783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_173503.4	c.38A>C	p.Asn13Thr	missense_variant	2/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2	c.194A>C	p.Asn65Thr	missense_variant	4/12		NP_001138405.1
EFCAB3	XM_011524381.3	c.104A>C	p.Asn35Thr	missense_variant	2/10		XP_011522683.2
EFCAB3	XM_011524380.2	c.38A>C	p.Asn13Thr	missense_variant	2/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8	c.38A>C	p.Asn13Thr	missense_variant	2/10	1	NM_173503.4	ENSP00000302649.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 20, 2024

The c.194A>C (p.N65T) alteration is located in exon 4 (coding exon 4) of the EFCAB3 gene. This alteration results from a A to C substitution at nucleotide position 194, causing the asparagine (N) at amino acid position 65 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	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	.;T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	.;M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.065	T;T;T;T
Sift4G	Benign	0.076	T;T;T;T
Polyphen		0.27	.;B;B;.
Vest4		0.24
MutPred		0.24		.;Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.77
MPC		0.27
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.098
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: chr17-60460378;