Genetic Variant CCDC12:p.Glu12Lys (chr3-46976699-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001277074.2(CCDC12):c.34G>A(p.Glu12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,604,696 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC12
NM_001277074.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Variant links:

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]

CCDC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC12	NM_001277074.2 link	c.34G>A	p.Glu12Lys	missense_variant	Exon 1 of 7	ENST00000683445.1	NP_001264003.1	Q8WUD4
CCDC12	NM_144716.6 link	c.73G>A	p.Glu25Lys	missense_variant	Exon 2 of 8		NP_653317.2	J3KR35
CCDC12	NR_102269.2 link	n.-198G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC12	ENST00000683445.1 link	c.34G>A	p.Glu12Lys	missense_variant	Exon 1 of 7		NM_001277074.2	ENSP00000508011.1		Q8WUD4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230434

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125070

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000973

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452440

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721854

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.66

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.86

D;D;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Uncertain

-0.040

MutationAssessor

Uncertain

2.7

M;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

.;D;.;.

REVEL

Benign

0.26

Sift

Benign

0.057

.;T;.;.

Sift4G

Uncertain

0.047

D;D;D;.

Polyphen

1.0

D;.;.;.

Vest4

0.49

MutPred

0.47

Gain of MoRF binding (P = 0.0045);.;Gain of MoRF binding (P = 0.0045);Gain of MoRF binding (P = 0.0045);

MVP

0.38

MPC

0.34

ClinPred

0.97

GERP RS

5.4

Varity_R

0.21

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over