X-126552372-C-T

Variant names:

• chrX-126552372-C-T
• rs150927042
• NM_178470.5:c.237G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_178470.5(DCAF12L1):​c.237G>A​(p.Ala79Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,574 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A79A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: DCAF12L1 NM_178470.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.572 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.237G>A	p.Ala79Ala	synonymous	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.237G>A	p.Ala79Ala	synonymous	Exon 1 of 2	ENSP00000360167.1	Q5VU92

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097574 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 2 AN XY: 363272

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19355

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40040

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

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 842043

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		-0.57
PromoterAI		0.039	Neutral
Mutation Taster		=100/0	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: rs150927042; hg19: chrX-125686355; COSMIC: COSV64423139;