10-12998371-G-C

Variant names:

• chr10-12998371-G-C
• rs754383912
• NM_031455.4:c.516C>G

Variant summary

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

The NM_031455.4(CCDC3):​c.516C>G​(p.Phe172Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CCDC3 NM_031455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

Genes affected

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
CCDC3	NM_031455.4	c.516C>G	p.Phe172Leu	missense_variant	Exon 2 of 3	ENST00000378825.5	NP_113643.1
CCDC3	NM_001282658.2	c.141C>G	p.Phe47Leu	missense_variant	Exon 6 of 7		NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378825.5	c.516C>G	p.Phe172Leu	missense_variant	Exon 2 of 3	1	NM_031455.4	ENSP00000368102.3
CCDC3	ENST00000378839.1	c.141C>G	p.Phe47Leu	missense_variant	Exon 6 of 7	2		ENSP00000368116.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33

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: 0.00000398 AC: 1 AN: 251316 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135810

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74350

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: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.97	D;.
Vest4		0.57
MutPred		0.33		Gain of sheet (P = 0.0036);.;
MVP		0.030
MPC		0.19
ClinPred		0.96	D
GERP RS		2.1
Varity_R		0.41
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs754383912; hg19: chr10-13040371;