chr17-62391847-C-G

Variant names:

• chr17-62391847-C-G
• rs2070305326
• NM_173503.4:c.177C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173503.4(EFCAB3):​c.177C>G​(p.Phe59Leu) 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 pathogenic 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: 1.16
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173503.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	NM_173503.4	MANE Select	c.177C>G	p.Phe59Leu	missense	Exon 4 of 10	NP_775774.1	Q8N7B9-1
	EFCAB3	NM_001144933.2		c.333C>G	p.Phe111Leu	missense	Exon 6 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000305286.8	TSL:1 MANE Select	c.177C>G	p.Phe59Leu	missense	Exon 4 of 10	ENSP00000302649.3	Q8N7B9-1
	EFCAB3	ENST00000450662.7	TSL:5	c.333C>G	p.Phe111Leu	missense	Exon 6 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000520404.5	TSL:5	c.177C>G	p.Phe59Leu	missense	Exon 4 of 7	ENSP00000429124.1	E5RJB7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.88		Loss of stability (P = 0.0621)
MVP		0.84
MPC		0.70
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.77
gMVP		0.49

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

Other links and lift over

dbSNP: rs2070305326; hg19: chr17-60469208;