Genetic Variant DCAF12L1:p.Val265Val (chrX-126551814-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_178470.5(DCAF12L1):c.795G>A(p.Val265Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,211,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V265V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

DCAF12L1
NM_178470.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

0 publications found

Variant links:

Genes affected

DCAF12L1 (HGNC:29395): (DDB1 and CUL4 associated factor 12 like 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

DCAF12L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=0.046 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178470.5. 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
	DCAF12L1	NM_178470.5	MANE Select	c.795G>A	p.Val265Val	synonymous	Exon 1 of 2	NP_848565.2	Q5VU92

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF12L1	ENST00000371126.3	TSL:1 MANE Select	c.795G>A	p.Val265Val	synonymous	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113121

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

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:

9.11e-7

AC:

AN:

1098060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363468

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40403

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842104

Other (OTH)

AF:

0.00

AC:

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113121

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35269

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31180

American (AMR)

AF:

0.00

AC:

AN:

10829

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2807

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6293

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53332

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.2

(source)

DANN

Benign

0.57

PhyloP100

0.046

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over