NM_001277074.2:c.10A>G

Variant names:

• chr3-46976723-T-C
• NM_001277074.2:c.10A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001277074.2(CCDC12):​c.10A>G​(p.Thr4Ala) 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. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: CCDC12 NM_001277074.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.42
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04070452).
• BP6: Variant 3-46976723-T-C is Benign according to our data. Variant chr3-46976723-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3138287.Status of the report is criteria_provided_single_submitter, 1 stars.

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.10A>G	p.Thr4Ala	missense	Exon 1 of 7	NP_001264003.1	Q8WUD4
	CCDC12	NM_144716.6		c.49A>G	p.Thr17Ala	missense	Exon 2 of 8	NP_653317.2	J3KR35
	CCDC12	NR_102269.2		n.-222A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000683445.1	MANE Select	c.10A>G	p.Thr4Ala	missense	Exon 1 of 7	ENSP00000508011.1	Q8WUD4
	CCDC12	ENST00000878135.1		c.10A>G	p.Thr4Ala	missense	Exon 1 of 8	ENSP00000548194.1
	CCDC12	ENST00000878137.1		c.10A>G	p.Thr4Ala	missense	Exon 1 of 8	ENSP00000548196.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.053
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0070
DANN	Benign	0.75
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-2.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.012
Sift	Benign	0.23	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.18		Gain of helix (P = 0.0093)
MVP		0.10
MPC		0.21
ClinPred		0.086	T
GERP RS		-4.7
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.11
Mutation Taster		=100/0	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: chr3-47018213;