Genetic Variant NM_178470.5:c.1363C>T (chrX-126551246-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178470.5(DCAF12L1):c.1363C>T(p.His455Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000438 in 1,208,982 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000031 ( 0 hom. 6 hem. )

Consequence

DCAF12L1
NM_178470.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.30

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043356).

BS2

High Hemizygotes in GnomAd4 at 7 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.1363C>T	p.His455Tyr	missense	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.1363C>T	p.His455Tyr	missense	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111639

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

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

GnomAD2 exomes

AF:

0.0000718

AC:

AN:

181134

AF XY:

0.0000304

show subpopulations

Gnomad AFR exome

AF:

0.000913

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1097289

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

362767

show subpopulations

African (AFR)

AF:

0.000948

AC:

AN:

26385

American (AMR)

AF:

0.0000284

AC:

AN:

35171

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19294

East Asian (EAS)

AF:

0.000132

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

53979

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40491

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4003

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841726

Other (OTH)

AF:

0.0000869

AC:

AN:

46034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000170

AC:

AN:

111693

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33867

show subpopulations

African (AFR)

AF:

0.000584

AC:

AN:

30809

American (AMR)

AF:

0.0000946

AC:

AN:

10568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3512

South Asian (SAS)

AF:

0.00

AC:

AN:

2660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53103

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000764

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.048

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0073

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.43

PhyloP100

6.3

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Benign

0.11

Sift

Benign

0.46

Sift4G

Benign

0.72

Polyphen

0.0020

Vest4

0.59

MVP

0.20

MPC

1.1

ClinPred

0.039

GERP RS

2.0

Varity_R

0.10

gMVP

0.91

Mutation Taster

=98/2

polymorphism

(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