rs763667428

Variant names:

• chrX-126164941-G-C
• rs763667428
• NM_001013628.3:c.984C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-126164941-G-C
• chrX-126164941-G-A
• chrX-126164941-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001013628.3(DCAF12L2):​c.984C>G​(p.His328Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: DCAF12L2 NM_001013628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.716
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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.984C>G	p.His328Gln	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.984C>G	p.His328Gln	missense	Exon 1 of 1	ENSP00000353128.2	Q5VW00

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182160 AF XY: 0.0000297

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: 0.0000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2 AN: 1097992 Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 2 AN XY: 363448

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40321

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 842095

Other (OTH) AF: 0.00 AC: 0 AN: 46092

GnomAD4 genome Cov.: 26

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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.51
DANN	Benign	0.92
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.72
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.36	B
Vest4		0.74
MutPred		0.75		Gain of disorder (P = 0.0678)
MVP		0.57
ClinPred		0.30	T
GERP RS		-8.1
Varity_R		0.29
gMVP		0.71
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs763667428; hg19: chrX-125298924;