rs1569107461

Variant names:

• chr22-43530927-G-A
• NM_022785.4:c.4271C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-43530927-G-A
• chr22-43530927-G-C

Variant summary

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

The NM_022785.4(EFCAB6):​c.4271C>T​(p.Ala1424Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1424G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EFCAB6 NM_022785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55

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)

ACMG classification

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 rank	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.4271C>T	p.Ala1424Val	missense_variant	Exon 31 of 32	ENST00000262726.12	NP_073622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB6	ENST00000262726.12	c.4271C>T	p.Ala1424Val	missense_variant	Exon 31 of 32	2	NM_022785.4	ENSP00000262726.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0029	.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.53
MutPred		0.33		.;Loss of disorder (P = 0.1139);
MVP		0.42
MPC		0.35
ClinPred		0.67	D
GERP RS		2.5
Varity_R		0.14
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr22-43926807;