chrX-126165218-T-A

Variant names:

• chrX-126165218-T-A
• rs771869601
• NM_001013628.3:c.707A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013628.3(DCAF12L2):​c.707A>T​(p.Glu236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,822 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: DCAF12L2 NM_001013628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

DCAF12L2 (HGNC:32950): (DDB1 and CUL4 associated factor 12 like 2) 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 multi-protein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 9. However, the CDS of this intronless gene remains intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056569308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013628.3. 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
	DCAF12L2	NM_001013628.3	MANE Select	c.707A>T	p.Glu236Val	missense	Exon 1 of 1	NP_001013650.1	Q5VW00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF12L2	ENST00000360028.4	TSL:6 MANE Select	c.707A>T	p.Glu236Val	missense	Exon 1 of 1	ENSP00000353128.2	Q5VW00

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181001 AF XY: 0.00

Gnomad AFR exome AF: 0.0000795

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: 9.11e-7 AC: 1 AN: 1097822 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 363218

African (AFR) AF: 0.0000379 AC: 1 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19366

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40323

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842007

Other (OTH) AF: 0.00 AC: 0 AN: 46080

GnomAD4 genome Cov.: 25

ExAC AF: 0.00000824 AC: 1

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	0.13
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.4
DANN	Benign	0.32
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.35	N
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.023
Sift	Benign	0.35	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.28		Gain of catalytic residue at S235 (P = 0.2496)
MVP		0.22
ClinPred		0.022	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.60
Mutation Taster		=96/4	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: rs771869601; hg19: chrX-125299201;