rs1013970712

Variant names:

• chr22-43537451-C-G
• rs1013970712
• NM_022785.4:c.3974G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-43537451-C-G
• chr22-43537451-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022785.4(EFCAB6):​c.3974G>C​(p.Trp1325Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: EFCAB6 NM_022785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB6	NM_022785.4	MANE Select	c.3974G>C	p.Trp1325Ser	missense	Exon 29 of 32	NP_073622.2
	EFCAB6	NM_198856.3		c.3518G>C	p.Trp1173Ser	missense	Exon 27 of 30	NP_942153.1	Q5THR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB6	ENST00000262726.12	TSL:2 MANE Select	c.3974G>C	p.Trp1325Ser	missense	Exon 29 of 32	ENSP00000262726.7	Q5THR3-1
	EFCAB6	ENST00000396231.6	TSL:1	c.3518G>C	p.Trp1173Ser	missense	Exon 27 of 30	ENSP00000379533.2	Q5THR3-2
	EFCAB6	ENST00000461800.5	TSL:1	n.611G>C		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32

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 Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.80		Gain of disorder (P = 1e-04)
MVP		0.55
MPC		0.44
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.91
gMVP		0.67
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs1013970712; hg19: chr22-43933331;