chr1-46683380-A-C

Variant names:

• chr1-46683380-A-C
• NM_014774.3:c.1232T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014774.3(EFCAB14):​c.1232T>G​(p.Phe411Cys) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB14 NM_014774.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

EFCAB14 (HGNC:29051): (EF-hand calcium binding domain 14) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB14-AS1 (HGNC:44108): (EFCAB14 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37320146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014774.3. 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
	EFCAB14	NM_014774.3	MANE Select	c.1232T>G	p.Phe411Cys	missense	Exon 10 of 11	NP_055589.1	O75071
	EFCAB14-AS1	NR_038827.1		n.268+1116A>C		intron	N/A
	EFCAB14-AS1	NR_038828.1		n.185-3293A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB14	ENST00000371933.8	TSL:1 MANE Select	c.1232T>G	p.Phe411Cys	missense	Exon 10 of 11	ENSP00000361001.3	O75071
	EFCAB14	ENST00000672422.2		c.1325T>G	p.Phe442Cys	missense	Exon 10 of 11	ENSP00000499873.2	A0A804H3B5
	EFCAB14	ENST00000674263.1		c.1232T>G	p.Phe411Cys	missense	Exon 10 of 12	ENSP00000501323.1	A0A6I8PIF8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.056
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.53
MutPred		0.20		Loss of stability (P = 0.0991)
MVP		0.46
MPC		0.52
ClinPred		0.87	D
GERP RS		2.9
Varity_R		0.082
gMVP		0.36
Mutation Taster		=92/8	polymorphism

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

hg19: chr1-47149052;