dbSNP rs149056465: DCAF12L1:p.Ala379Ala (chrX-126551472-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_178470.5(DCAF12L1):c.1137C>T(p.Ala379Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,209,939 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,389 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., 109 hem., cov: 24)

Exomes 𝑓: 0.0066 ( 17 hom. 2280 hem. )

Consequence

DCAF12L1
NM_178470.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Publications

1 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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant X-126551472-G-A is Benign according to our data. Variant chrX-126551472-G-A is described in ClinVar as Benign. ClinVar VariationId is 774365.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 109 gene

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.1137C>T	p.Ala379Ala	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.1137C>T	p.Ala379Ala	synonymous	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

428

AN:

111778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00442

Gnomad AMR

AF:

0.000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00463

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.00267

GnomAD2 exomes

AF:

0.00409

AC:

747

AN:

182802

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00613

Gnomad NFE exome

AF:

0.00742

Gnomad OTH exome

AF:

0.00532

GnomAD4 exome

AF:

0.00662

AC:

7273

AN:

1098106

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

2280

AN XY:

363504

show subpopulations

African (AFR)

AF:

0.000492

AC:

AN:

26401

American (AMR)

AF:

0.000540

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.000155

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000129

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.00686

AC:

277

AN:

40399

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00799

AC:

6732

AN:

842136

Other (OTH)

AF:

0.00482

AC:

222

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

368

736

1105

1473

1841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.00383

AC:

428

AN:

111833

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

109

AN XY:

34015

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

30834

American (AMR)

AF:

0.000658

AC:

AN:

10632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3516

South Asian (SAS)

AF:

0.00

AC:

AN:

2657

European-Finnish (FIN)

AF:

0.00463

AC:

AN:

6045

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00667

AC:

354

AN:

53087

Other (OTH)

AF:

0.00264

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00402

Hom.:

Bravo

AF:

0.00340

EpiCase

AF:

0.00649

EpiControl

AF:

0.00593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.0

(source)

DANN

Benign

0.47

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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