NM_018100.4:c.1224C>G

Variant names:

• chr6-52469419-C-G
• NM_018100.4:c.1224C>G

Variant summary

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

The NM_018100.4(EFHC1):​c.1224C>G​(p.Asp408Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468

Genes affected

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.1224C>G	p.Asp408Glu	missense_variant	Exon 7 of 11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.1167C>G	p.Asp389Glu	missense_variant	Exon 8 of 12		NP_001165891.1
EFHC1	NR_033327.2	n.2550C>G		non_coding_transcript_exon_variant	Exon 6 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.1224C>G	p.Asp408Glu	missense_variant	Exon 7 of 11	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727170

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.56
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;T;T;T;T;T;T;.;T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D;D;D;D;D;.;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Pathogenic	3.4	.;.;.;M;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	.;.;.;D;.;.;.;.;.;.;.;.;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0040	.;.;.;D;.;.;.;.;.;.;.;.;D
Sift4G	Uncertain	0.011	.;.;.;D;.;.;.;.;.;.;.;.;D
Polyphen		1.0	.;.;.;D;.;.;.;.;.;.;.;.;.
Vest4		0.60, 0.59
MutPred		0.70		.;.;.;Gain of methylation at K406 (P = 0.0848);Gain of methylation at K406 (P = 0.0848);Gain of methylation at K406 (P = 0.0848);Gain of methylation at K406 (P = 0.0848);Gain of methylation at K406 (P = 0.0848);.;Gain of methylation at K406 (P = 0.0848);.;.;.;
MVP		0.82
MPC		0.43
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.43
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-52334217;