3-46976711-C-T

Position:

• chr3-46976711-C-T

Variant summary

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

The NM_001277074.2(CCDC12):​c.22G>A​(p.Val8Met) 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. 11/19 in silico tools predict 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: 35)
• Consequence: CCDC12 NM_001277074.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

Genes affected

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23586428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC12	NM_001277074.2	c.22G>A	p.Val8Met	missense_variant	1/7	ENST00000683445.1	NP_001264003.1
CCDC12	NM_144716.6	c.61G>A	p.Val21Met	missense_variant	2/8		NP_653317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC12	ENST00000683445.1	c.22G>A	p.Val8Met	missense_variant	1/7		NM_001277074.2	ENSP00000508011.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 35

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

Oct 11, 2024

The c.61G>A (p.V21M) alteration is located in exon 1 (coding exon 1) of the CCDC12 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the valine (V) at amino acid position 21 to be replaced by a methionine (M). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.;T;T
Eigen	Benign	0.021
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	.;N;.;.
REVEL	Benign	0.070
Sift	Uncertain	0.0020	.;D;.;.
Sift4G	Uncertain	0.0060	D;D;D;.
Polyphen		0.59	P;.;.;.
Vest4		0.24
MutPred		0.19		Gain of glycosylation at T5 (P = 0.0313);.;Gain of glycosylation at T5 (P = 0.0313);Gain of glycosylation at T5 (P = 0.0313);
MVP		0.21
MPC		0.24
ClinPred		0.92	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.22

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: chr3-47018201;