ENST00000425441.5:c.-21G>T

Variant names:

• chr3-46976753-C-A
• rs777140774
• ENST00000878135.1:c.-21G>T

Variant summary

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

The ENST00000425441.5(CCDC12):​c.-21G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,440,484 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CCDC12 ENST00000425441.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425441.5. 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>T	p.Gly7*	stop_gained	Exon 2 of 8	NP_653317.2	J3KR35
	CCDC12	NM_001277074.2	MANE Select	c.-21G>T		upstream_gene	N/A	NP_001264003.1	Q8WUD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000878135.1		c.-21G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000548194.1
	CCDC12	ENST00000878137.1		c.-21G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000548196.1
	CCDC12	ENST00000718454.1		c.-21G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000520832.1	A0ABB0MVG9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000954 AC: 2 AN: 209620 AF XY: 0.0000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000417 AC: 6 AN: 1440484 Hom.: 0 Cov.: 34 AF XY: 0.00000420 AC XY: 3 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: 0.000131 AC: 5 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: 9.07e-7 AC: 1 AN: 1101952

Other (OTH) AF: 0.00 AC: 0 AN: 59662

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Uncertain	0.090
CADD	Benign	12
DANN	Uncertain	0.98
Eigen	Uncertain	0.46
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.061	N
PhyloP100		2.0
Vest4		0.12
GERP RS		3.8
PromoterAI		-0.32	Neutral
Mutation Taster		=94/106	disease causing (fs/PTC)

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

dbSNP: rs777140774; hg19: chr3-47018243;