Variant 9-34098404-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015397.4(DCAF12):c.715G>A(p.Ala239Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

DCAF12
NM_015397.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

DCAF12 (HGNC:19911): (DDB1 and CUL4 associated factor 12) This gene encodes a WD repeat-containing protein that interacts with the COP9 signalosome, a macromolecular complex that interacts with cullin-RING E3 ligases and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. [provided by RefSeq, Jul 2009]

DCAF12 links:

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=0.33775014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12	NM_015397.4 linkuse as main transcript	c.715G>A	p.Ala239Thr	missense_variant	5/9	ENST00000361264.9	NP_056212.1	Q5T6F0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9 linkuse as main transcript	c.715G>A	p.Ala239Thr	missense_variant	5/9	1	NM_015397.4	ENSP00000355114.3		Q5T6F0
DCAF12	ENST00000396990.6 linkuse as main transcript	c.661G>A	p.Ala221Thr	missense_variant	5/5	3		ENSP00000380187.2		X6RBJ8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251404

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

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:

0.00000378

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.715G>A (p.A239T) alteration is located in exon 5 (coding exon 5) of the DCAF12 gene. This alteration results from a G to A substitution at nucleotide position 715, causing the alanine (A) at amino acid position 239 to be replaced by a threonine (T). 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

0.21

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0076

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.14

Sift

Benign

0.61

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.94

P;.

Vest4

0.58

MutPred

0.29

Gain of ubiquitination at K238 (P = 0.1245);.;

MVP

0.75

MPC

0.83

ClinPred

0.87

GERP RS

5.5

Varity_R

0.13

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over