X-126551915-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
Variant links:
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]

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ACMG classification

Classification made for transcript

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
DCAF12L1NM_178470.5 linkc.694G>T p.Ala232Ser missense_variant Exon 1 of 2 ENST00000371126.3 NP_848565.2 Q5VU92

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCAF12L1ENST00000371126.3 linkc.694G>T p.Ala232Ser missense_variant Exon 1 of 2 1 NM_178470.5 ENSP00000360167.1 Q5VU92

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
LINK: link

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; API