rs137852780

Variant names:

• chr6-52454147-G-A
• rs137852780
• NM_018100.4:c.776G>A

Variant summary

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

The NM_018100.4(EFHC1):​c.776G>A​(p.Cys259Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.32

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

Our verdict: Uncertain_significance. The variant received 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.776G>A	p.Cys259Tyr	missense_variant	Exon 5 of 11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.719G>A	p.Cys240Tyr	missense_variant	Exon 6 of 12		NP_001165891.1
EFHC1	NR_033327.2	n.2102G>A		non_coding_transcript_exon_variant	Exon 4 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.776G>A	p.Cys259Tyr	missense_variant	Exon 5 of 11	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Absence seizure Other:1

Dec 12, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;.;.;T;T;T;T;T;T;.;T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D;D;.;D;D;D;D;D;D;D;D;.;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.79	.;.;.;N;.;.;.;.;.;.;.;.;.
PhyloP100		2.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	.;.;.;N;.;.;.;.;.;.;.;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.18	.;.;.;T;.;.;.;.;.;.;.;.;T
Sift4G	Benign	0.081	.;.;.;T;.;.;.;.;.;.;.;.;T
Polyphen		0.27	.;.;.;B;.;.;.;.;.;.;.;.;.
Vest4		0.15, 0.15
MutPred		0.76		.;.;.;Loss of catalytic residue at T261 (P = 0.1845);Loss of catalytic residue at T261 (P = 0.1845);Loss of catalytic residue at T261 (P = 0.1845);Loss of catalytic residue at T261 (P = 0.1845);Loss of catalytic residue at T261 (P = 0.1845);.;Loss of catalytic residue at T261 (P = 0.1845);.;.;.;
MVP		0.83
MPC		0.20
ClinPred		0.40	T
GERP RS		5.9
Varity_R		0.12
gMVP		0.48
Mutation Taster		=4/96	disease causing

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

LitVar

Other links and lift over

dbSNP: rs137852780; hg19: chr6-52318945;