3-46976753-C-G

Variant names:

• chr3-46976753-C-G
• rs777140774
• NM_144716.6:c.19G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144716.6(CCDC12):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC12 NM_144716.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• 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=0.1331054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144716.6. 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_144716.6		c.19G>C	p.Gly7Arg	missense	Exon 2 of 8	NP_653317.2	J3KR35
	CCDC12	NM_001277074.2	MANE Select	c.-21G>C		upstream_gene	N/A	NP_001264003.1	Q8WUD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000292314.6	TSL:5	c.19G>C	p.Gly7Arg	missense	Exon 2 of 8	ENSP00000292314.2	J3KR35
	CCDC12	ENST00000878135.1		c.-21G>C		5_prime_UTR	Exon 1 of 8	ENSP00000548194.1
	CCDC12	ENST00000878137.1		c.-21G>C		5_prime_UTR	Exon 1 of 8	ENSP00000548196.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 209620 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440484 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 714790

African (AFR) AF: 0.00 AC: 0 AN: 32798

American (AMR) AF: 0.00 AC: 0 AN: 41610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25722

East Asian (EAS) AF: 0.00 AC: 0 AN: 38126

South Asian (SAS) AF: 0.00 AC: 0 AN: 83130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101952

Other (OTH) AF: 0.0000168 AC: 1 AN: 59662

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Vest4		0.41
MutPred		0.28		Gain of MoRF binding (P = 5e-04)
MVP		0.12
ClinPred		0.95	D
GERP RS		3.8
PromoterAI		-0.19	Neutral
gMVP		0.054
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs777140774; hg19: chr3-47018243;