22-43534842-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022785.4(EFCAB6):​c.4079G>A​(p.Ser1360Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EFCAB6
NM_022785.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.640
Variant links:
Genes affected
EFCAB6 (HGNC:24204): (EF-hand calcium binding domain 6) This gene encodes a protein which directly binds the oncogene DJ-1 and androgen receptor to form a ternary complex in cells. This binding protein recruits histone-deacetylase complexes in order to repress transcription activity of androgen receptor. This protein may also play a role in spermatogenesis and fertilization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10402128).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EFCAB6NM_022785.4 linkuse as main transcriptc.4079G>A p.Ser1360Asn missense_variant 30/32 ENST00000262726.12 NP_073622.2 Q5THR3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EFCAB6ENST00000262726.12 linkuse as main transcriptc.4079G>A p.Ser1360Asn missense_variant 30/322 NM_022785.4 ENSP00000262726.7 Q5THR3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243786
Hom.:
0
AF XY:
0.00000760
AC XY:
1
AN XY:
131532
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000894
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455596
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
723666
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJul 30, 2023The c.4079G>A (p.S1360N) alteration is located in exon 30 (coding exon 28) of the EFCAB6 gene. This alteration results from a G to A substitution at nucleotide position 4079, causing the serine (S) at amino acid position 1360 to be replaced by an asparagine (N). 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
0.13
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
13
DANN
Benign
0.91
DEOGEN2
Benign
0.0034
.;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.65
.;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.50
N;N
REVEL
Benign
0.097
Sift
Benign
0.16
T;T
Sift4G
Benign
0.25
T;T
Polyphen
0.028
.;B
Vest4
0.16
MutPred
0.42
.;Loss of stability (P = 0.0936);
MVP
0.16
MPC
0.059
ClinPred
0.060
T
GERP RS
2.0
Varity_R
0.055
gMVP
0.091

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

LitVar

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

Other links and lift over

dbSNP: rs756773886; hg19: chr22-43930722; API