10-12898432-G-A

Variant names:

• chr10-12898432-G-A
• rs116856516
• NM_031455.4:c.797C>T

Variant summary

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

The NM_031455.4(CCDC3):​c.797C>T​(p.Pro266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,603,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P266R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CCDC3 NM_031455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 6 publications found

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]

ENSG00000285520 (HGNC:):

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=0.16486025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031455.4. 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
	CCDC3	NM_031455.4	MANE Select	c.797C>T	p.Pro266Leu	missense	Exon 3 of 3	NP_113643.1	Q9BQI4-1
	CCDC3	NM_001282658.2		c.422C>T	p.Pro141Leu	missense	Exon 7 of 7	NP_001269587.1	Q9BQI4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	ENST00000378825.5	TSL:1 MANE Select	c.797C>T	p.Pro266Leu	missense	Exon 3 of 3	ENSP00000368102.3	Q9BQI4-1
	CCDC3	ENST00000870347.1		c.776C>T	p.Pro259Leu	missense	Exon 3 of 3	ENSP00000540406.1
	CCDC3	ENST00000378839.1	TSL:2	c.422C>T	p.Pro141Leu	missense	Exon 7 of 7	ENSP00000368116.1	Q9BQI4-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239566 AF XY: 0.00000762

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: 0.00000935

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000827 AC: 12 AN: 1451138 Hom.: 0 Cov.: 48 AF XY: 0.00000833 AC XY: 6 AN XY: 720250

African (AFR) AF: 0.00 AC: 0 AN: 33026

American (AMR) AF: 0.0000227 AC: 1 AN: 44028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 85836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52586

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 5006

European-Non Finnish (NFE) AF: 0.00000814 AC: 9 AN: 1105498

Other (OTH) AF: 0.00 AC: 0 AN: 59790

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 35 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 20

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.6
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.073
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		0.013	B
Vest4		0.16
MutPred		0.34		Gain of MoRF binding (P = 0.0168)
MVP		0.014
MPC		0.11
ClinPred		0.35	T
GERP RS		2.8
Varity_R		0.13
gMVP		0.17
Mutation Taster		=97/3	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

dbSNP: rs116856516; hg19: chr10-12940432; COSMIC: COSV66559710;