X-44235338-T-A

Variant summary

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

The ENST00000420999.2(EFHC2):​c.1390A>T​(p.Ile464Phe) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

EFHC2
ENST00000420999.2 missense

Scores

5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.376
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
EFHC2NM_025184.4 linkuse as main transcriptc.1390A>T p.Ile464Phe missense_variant 9/15 ENST00000420999.2 NP_079460.2
EFHC2XM_047442535.1 linkuse as main transcriptc.1390A>T p.Ile464Phe missense_variant 9/14 XP_047298491.1
EFHC2XM_047442536.1 linkuse as main transcriptc.1390A>T p.Ile464Phe missense_variant 9/15 XP_047298492.1
EFHC2XM_006724562.3 linkuse as main transcriptc.802A>T p.Ile268Phe missense_variant 8/14 XP_006724625.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EFHC2ENST00000420999.2 linkuse as main transcriptc.1390A>T p.Ile464Phe missense_variant 9/151 NM_025184.4 ENSP00000404232 P1Q5JST6-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
23

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 submitterclinical testingAmbry GeneticsJun 07, 2024The c.1390A>T (p.I464F) alteration is located in exon 9 (coding exon 9) of the EFHC2 gene. This alteration results from a A to T substitution at nucleotide position 1390, causing the isoleucine (I) at amino acid position 464 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
8.3
DANN
Benign
0.95
DEOGEN2
Benign
0.032
T
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.035
D
MetaRNN
Uncertain
0.50
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
REVEL
Uncertain
0.30
Sift4G
Uncertain
0.058
T
Polyphen
0.49
P
Vest4
0.63
MutPred
0.57
Loss of sheet (P = 0.1501);
MVP
0.52
MPC
0.30
ClinPred
0.33
T
GERP RS
-0.079
Varity_R
0.27
gMVP
0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-44094584; API