chrX-126552550-G-A

Variant names:

• chrX-126552550-G-A
• rs1391416107
• NM_178470.5:c.59C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_178470.5(DCAF12L1):​c.59C>T​(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,094,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 3 hem.)
• Consequence: DCAF12L1 NM_178470.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.503
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1725379).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.59C>T	p.Ala20Val	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.59C>T	p.Ala20Val	missense	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 169937 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000128 AC: 14 AN: 1094287 Hom.: 0 Cov.: 32 AF XY: 0.00000830 AC XY: 3 AN XY: 361483

African (AFR) AF: 0.00 AC: 0 AN: 26365

American (AMR) AF: 0.00 AC: 0 AN: 35151

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19325

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 54085

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3891

European-Non Finnish (NFE) AF: 0.0000166 AC: 14 AN: 841798

Other (OTH) AF: 0.00 AC: 0 AN: 46001

GnomAD4 genome Cov.: 23

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	Benign	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.50
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.067
Sift	Benign	0.12	T
Sift4G	Benign	0.49	T
Polyphen		1.0	D
Vest4		0.070
MutPred		0.15		Loss of glycosylation at S25 (P = 0.1768)
MVP		0.42
MPC		1.8
ClinPred		0.44	T
GERP RS		2.3
PromoterAI		-0.094	Neutral
Varity_R		0.064
gMVP		0.63
Mutation Taster		=99/1	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: rs1391416107; hg19: chrX-125686533; COSMIC: COSV100948450;