3-46976711-C-T

Variant names:

• chr3-46976711-C-T
• NM_001277074.2:c.22G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: CCDC12 NM_001277074.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23586428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277074.2. 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
	CCDC12	NM_001277074.2	MANE Select	c.22G>A	p.Val8Met	missense	Exon 1 of 7	NP_001264003.1	Q8WUD4
	CCDC12	NM_144716.6		c.61G>A	p.Val21Met	missense	Exon 2 of 8	NP_653317.2	J3KR35
	CCDC12	NR_102269.2		n.-210G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000683445.1	MANE Select	c.22G>A	p.Val8Met	missense	Exon 1 of 7	ENSP00000508011.1	Q8WUD4
	CCDC12	ENST00000878135.1		c.22G>A	p.Val8Met	missense	Exon 1 of 8	ENSP00000548194.1
	CCDC12	ENST00000878137.1		c.22G>A	p.Val8Met	missense	Exon 1 of 8	ENSP00000548196.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.021
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.59	P
Vest4		0.24
MutPred		0.19		Gain of glycosylation at T5 (P = 0.0313)
MVP		0.21
MPC		0.24
ClinPred		0.92	D
GERP RS		4.5
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.22
Mutation Taster		=81/19	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

hg19: chr3-47018201;