NM_178470.5:c.230G>A

Variant names:

• chrX-126552379-C-T
• rs1304079076
• NM_178470.5:c.230G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178470.5(DCAF12L1):​c.230G>A​(p.Gly77Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,519 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: DCAF12L1 NM_178470.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27746832).

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.230G>A	p.Gly77Asp	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.230G>A	p.Gly77Asp	missense	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097519 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363245

African (AFR) AF: 0.0000379 AC: 1 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40035

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842004

Other (OTH) AF: 0.0000434 AC: 2 AN: 46089

GnomAD4 genome Cov.: 24

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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.9
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Benign	0.24	T
Polyphen		0.65	P
Vest4		0.46
MutPred		0.53		Loss of methylation at R76 (P = 0.0438)
MVP		0.39
MPC		1.2
ClinPred		0.14	T
GERP RS		1.8
PromoterAI		0.020	Neutral
Varity_R		0.16
gMVP		0.76
Mutation Taster		=95/5	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: rs1304079076; hg19: chrX-125686362;