Menu
GeneBe

X-44248815-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_025184.4(EFHC2):c.960C>T(p.Phe320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000747 in 1,204,477 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 4 hem., cov: 23)
Exomes 𝑓: 0.000077 ( 0 hom. 34 hem. )

Consequence

EFHC2
NM_025184.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.587
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 Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-44248815-G-A is Benign according to our data. Variant chrX-44248815-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660365.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.587 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EFHC2NM_025184.4 linkuse as main transcriptc.960C>T p.Phe320= synonymous_variant 6/15 ENST00000420999.2
EFHC2XM_047442535.1 linkuse as main transcriptc.960C>T p.Phe320= synonymous_variant 6/14
EFHC2XM_047442536.1 linkuse as main transcriptc.960C>T p.Phe320= synonymous_variant 6/15
EFHC2XM_006724562.3 linkuse as main transcriptc.372C>T p.Phe124= synonymous_variant 5/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EFHC2ENST00000420999.2 linkuse as main transcriptc.960C>T p.Phe320= synonymous_variant 6/151 NM_025184.4 P1Q5JST6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000539
AC:
6
AN:
111287
Hom.:
0
Cov.:
23
AF XY:
0.000119
AC XY:
4
AN XY:
33481
show subpopulations
Gnomad AFR
AF:
0.000131
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000449
AC:
8
AN:
178009
Hom.:
0
AF XY:
0.0000623
AC XY:
4
AN XY:
64185
show subpopulations
Gnomad AFR exome
AF:
0.000247
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000546
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000502
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000768
AC:
84
AN:
1093190
Hom.:
0
Cov.:
28
AF XY:
0.0000947
AC XY:
34
AN XY:
358870
show subpopulations
Gnomad4 AFR exome
AF:
0.000152
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000559
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000847
Gnomad4 OTH exome
AF:
0.000131
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000539
AC:
6
AN:
111287
Hom.:
0
Cov.:
23
AF XY:
0.000119
AC XY:
4
AN XY:
33481
show subpopulations
Gnomad4 AFR
AF:
0.000131
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
1
Bravo
AF:
0.0000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023EFHC2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
2.7
Dann
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372092672; hg19: chrX-44108061; COSMIC: COSV69554555; API