X-126551915-C-A

Variant names:

• chrX-126551915-C-A
• NM_178470.5:c.694G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178470.5(DCAF12L1):​c.694G>T​(p.Ala232Ser) 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 benign outcome for this variant. 15/20 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)
• Consequence: DCAF12L1 NM_178470.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0490

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0824877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF12L1	NM_178470.5	c.694G>T	p.Ala232Ser	missense_variant	Exon 1 of 2	ENST00000371126.3	NP_848565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF12L1	ENST00000371126.3	c.694G>T	p.Ala232Ser	missense_variant	Exon 1 of 2	1	NM_178470.5	ENSP00000360167.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694G>T (p.A232S) alteration is located in exon 1 (coding exon 1) of the DCAF12L1 gene. This alteration results from a G to T substitution at nucleotide position 694, causing the alanine (A) at amino acid position 232 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.1
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.048
Sift	Benign	0.17	T
Sift4G	Benign	0.56	T
Polyphen		0.024	B
Vest4		0.071
MutPred		0.38		Loss of catalytic residue at A232 (P = 0.0071);
MVP		0.40
MPC		0.84
ClinPred		0.059	T
GERP RS		3.0
Varity_R		0.065
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-125685898;