22-43537477-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022785.4(EFCAB6):​c.3948G>C​(p.Arg1316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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 Likely benign in ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

EFCAB6
NM_022785.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.850
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]
EFCAB6-AS1 (HGNC:39999): (EFCAB6 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29805863).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EFCAB6NM_022785.4 linkc.3948G>C p.Arg1316Ser missense_variant Exon 29 of 32 ENST00000262726.12 NP_073622.2 Q5THR3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EFCAB6ENST00000262726.12 linkc.3948G>C p.Arg1316Ser missense_variant Exon 29 of 32 2 NM_022785.4 ENSP00000262726.7 Q5THR3-1
EFCAB6ENST00000396231.6 linkc.3492G>C p.Arg1164Ser missense_variant Exon 27 of 30 1 ENSP00000379533.2 Q5THR3-2
EFCAB6ENST00000461800.5 linkn.585G>C non_coding_transcript_exon_variant Exon 4 of 7 1
EFCAB6-AS1ENST00000656483.1 linkn.248+18880C>G intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461886
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0025
.;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.072
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
0.32
.;B
Vest4
0.17
MutPred
0.74
.;Loss of MoRF binding (P = 0.0392);
MVP
0.36
MPC
0.076
ClinPred
0.69
D
GERP RS
4.7
Varity_R
0.14
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs143251330; hg19: chr22-43933357; API