NM_014774.3:c.650A>T

Variant names:

• chr1-46691867-T-A
• NM_014774.3:c.650A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014774.3(EFCAB14):​c.650A>T​(p.Asp217Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,320 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EFCAB14 NM_014774.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.650A>T	p.Asp217Val	missense	Exon 5 of 11	NP_055589.1	O75071
	EFCAB14-AS1	NR_038827.1		n.360-7T>A		splice_region intron	N/A
	EFCAB14-AS1	NR_038828.1		n.276-7T>A		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB14	ENST00000371933.8	TSL:1 MANE Select	c.650A>T	p.Asp217Val	missense	Exon 5 of 11	ENSP00000361001.3	O75071
	EFCAB14	ENST00000672422.2		c.743A>T	p.Asp248Val	missense	Exon 5 of 11	ENSP00000499873.2	A0A804H3B5
	EFCAB14	ENST00000674263.1		c.650A>T	p.Asp217Val	missense	Exon 5 of 12	ENSP00000501323.1	A0A6I8PIF8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461320 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726962

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111710

Other (OTH) AF: 0.0000331 AC: 2 AN: 60352

GnomAD4 genome Cov.: 33

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	0.18
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.64
Sift	Benign	0.031	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.28		Gain of catalytic residue at D217 (P = 0.0436)
MVP		0.85
MPC		0.68
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.34
gMVP		0.23
Mutation Taster		=75/25	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: chr1-47157539;