22-43540326-T-C

Variant summary

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

The NM_022785.4(EFCAB6):ā€‹c.3680A>Gā€‹(p.Asn1227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,042 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

EFCAB6
NM_022785.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500
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=0.307602).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EFCAB6NM_022785.4 linkuse as main transcriptc.3680A>G p.Asn1227Ser missense_variant 28/32 ENST00000262726.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EFCAB6ENST00000262726.12 linkuse as main transcriptc.3680A>G p.Asn1227Ser missense_variant 28/322 NM_022785.4 P1Q5THR3-1
EFCAB6ENST00000396231.6 linkuse as main transcriptc.3224A>G p.Asn1075Ser missense_variant 26/301 Q5THR3-2
EFCAB6ENST00000461800.5 linkuse as main transcriptn.317A>G non_coding_transcript_exon_variant 3/71
EFCAB6-AS1ENST00000656483.1 linkuse as main transcriptn.249-18291T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152186
Hom.:
0
Cov.:
33
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251452
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135916
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:
0.0000352
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461856
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727236
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:
0.0000414
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152186
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
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:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsMar 17, 2023The c.3680A>G (p.N1227S) alteration is located in exon 28 (coding exon 26) of the EFCAB6 gene. This alteration results from a A to G substitution at nucleotide position 3680, causing the asparagine (N) at amino acid position 1227 to be replaced by a serine (S). 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
0.10
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0048
.;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.1
.;M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.3
N;N
REVEL
Uncertain
0.35
Sift
Benign
0.030
D;D
Sift4G
Benign
0.066
T;T
Polyphen
0.85
.;P
Vest4
0.29
MutPred
0.65
.;Loss of solvent accessibility (P = 0.0576);
MVP
0.75
MPC
0.086
ClinPred
0.15
T
GERP RS
2.1
Varity_R
0.24
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs776584159; hg19: chr22-43936206; API