rs137852781

Positions:

• chr6-52454254-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_018100.4(EFHC1):​c.883C>T​(p.Gln295Ter) variant causes a stop gained change. 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 risk factor (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFHC1 NM_018100.4 stop_gained
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 4.55

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.883C>T	p.Gln295Ter	stop_gained	5/11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.826C>T	p.Gln276Ter	stop_gained	6/12		NP_001165891.1
EFHC1	NR_033327.2	n.2209C>T		non_coding_transcript_exon_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.883C>T	p.Gln295Ter	stop_gained	5/11	1	NM_018100.4	ENSP00000360107	P1

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

Myoclonic epilepsy, juvenile, susceptibility to, 1 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 27, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.93	D
MutationTaster	Benign	1.0	A;A;A
Vest4		0.81, 0.81
GERP RS		5.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs137852781; hg19: chr6-52319052;