9-34088471-A-C

Position:

• chr9-34088471-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015397.4(DCAF12):​c.1241T>G​(p.Ile414Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: DCAF12 NM_015397.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06

Genes affected

DCAF12 (HGNC:19911): (DDB1 and CUL4 associated factor 12) This gene encodes a WD repeat-containing protein that interacts with the COP9 signalosome, a macromolecular complex that interacts with cullin-RING E3 ligases and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. [provided by RefSeq, Jul 2009]

ENSG00000228352 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34599155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12	NM_015397.4	c.1241T>G	p.Ile414Ser	missense_variant	9/9	ENST00000361264.9	NP_056212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9	c.1241T>G	p.Ile414Ser	missense_variant	9/9	1	NM_015397.4	ENSP00000355114.3
ENSG00000228352	ENST00000448245.1	n.82-1334A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2024

The c.1241T>G (p.I414S) alteration is located in exon 9 (coding exon 9) of the DCAF12 gene. This alteration results from a T to G substitution at nucleotide position 1241, causing the isoleucine (I) at amino acid position 414 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	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.024
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.22	T
Polyphen		0.59	P
Vest4		0.54
MutPred		0.44		Gain of glycosylation at I414 (P = 0.0155);
MVP		0.68
MPC		1.4
ClinPred		0.88	D
GERP RS		4.2
Varity_R		0.26
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34088469;