17-62391930-A-G

Position:

• chr17-62391930-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000305286.8(EFCAB3):​c.260A>G​(p.Asp87Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFCAB3 ENST00000305286.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_173503.4	c.260A>G	p.Asp87Gly	missense_variant	4/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2	c.416A>G	p.Asp139Gly	missense_variant	6/12		NP_001138405.1
EFCAB3	XM_011524381.3	c.326A>G	p.Asp109Gly	missense_variant	4/10		XP_011522683.2
EFCAB3	XM_011524380.2	c.260A>G	p.Asp87Gly	missense_variant	4/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8	c.260A>G	p.Asp87Gly	missense_variant	4/10	1	NM_173503.4	ENSP00000302649	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459340 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726006

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Feb 27, 2024

The c.416A>G (p.D139G) alteration is located in exon 6 (coding exon 6) of the EFCAB3 gene. This alteration results from a A to G substitution at nucleotide position 416, causing the aspartic acid (D) at amino acid position 139 to be replaced by a glycine (G). 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	0.27
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.;.
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.00067
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Uncertain	0.023	D
MutationAssessor	Uncertain	2.1	.;M;.;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.025, 0.94	.;B;P;.
Vest4		0.64
MutPred		0.65		.;Gain of methylation at K85 (P = 0.0485);Gain of methylation at K85 (P = 0.0485);Gain of methylation at K85 (P = 0.0485);
MVP		0.86
MPC		0.69
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.28
gMVP		0.52

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: chr17-60469291;