6-52454168-AC-GT

Variant names:

• chr6-52454168-AC-GT
• NM_018100.4:c.797_798delACinsGT
• EFHC1 p.Tyr266Cys

Variant summary

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

The NM_018100.4(EFHC1):​c.797_798delACinsGT​(p.Tyr266Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

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]

EFHC1 Gene-Disease associations (from GenCC):

• juvenile myoclonic epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018100.4. 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
	EFHC1	NM_018100.4	MANE Select	c.797_798delACinsGT	p.Tyr266Cys	missense	N/A	NP_060570.2	Q5JVL4-1
	EFHC1	NM_001172420.2		c.740_741delACinsGT	p.Tyr247Cys	missense	N/A	NP_001165891.1	Q5JVL4-3
	EFHC1	NR_033327.2		n.2123_2124delACinsGT		non_coding_transcript_exon	Exon 4 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	ENST00000371068.11	TSL:1 MANE Select	c.797_798delACinsGT	p.Tyr266Cys	missense	N/A	ENSP00000360107.4	Q5JVL4-1
	EFHC1	ENST00000637340.1	TSL:1	n.2722_2723delACinsGT		non_coding_transcript_exon	Exon 4 of 10
	EFHC1	ENST00000637353.1	TSL:5	c.797_798delACinsGT	p.Tyr266Cys	missense	N/A	ENSP00000490441.1	A0A1B0GVB0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-52318966;