X-44248304-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000420999.2(EFHC2):c.1079C>T(p.Thr360Met) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
EFHC2
ENST00000420999.2 missense
ENST00000420999.2 missense
Scores
8
6
1
Clinical Significance
Conservation
PhyloP100: 5.85
Genes affected
EFHC2 (HGNC:26233): (EF-hand domain containing 2) This gene encodes a protein which contains three DM10 domains and three calcium-binding EF-hand motifs. A related protein is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy (PMID: 15258581, 16112844) and that this gene may be associated with fear recognition in individuals with Turner syndrome. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.778
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EFHC2 | NM_025184.4 | c.1079C>T | p.Thr360Met | missense_variant | 7/15 | ENST00000420999.2 | NP_079460.2 | |
EFHC2 | XM_047442535.1 | c.1079C>T | p.Thr360Met | missense_variant | 7/14 | XP_047298491.1 | ||
EFHC2 | XM_047442536.1 | c.1079C>T | p.Thr360Met | missense_variant | 7/15 | XP_047298492.1 | ||
EFHC2 | XM_006724562.3 | c.491C>T | p.Thr164Met | missense_variant | 6/14 | XP_006724625.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EFHC2 | ENST00000420999.2 | c.1079C>T | p.Thr360Met | missense_variant | 7/15 | 1 | NM_025184.4 | ENSP00000404232.2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.1079C>T (p.T360M) alteration is located in exon 7 (coding exon 7) of the EFHC2 gene. This alteration results from a C to T substitution at nucleotide position 1079, causing the threonine (T) at amino acid position 360 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
REVEL
Pathogenic
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of phosphorylation at T360 (P = 0.0248);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at