10-12898432-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031455.4(CCDC3):​c.797C>A​(p.Pro266His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,603,364 control chromosomes in the GnomAD database, including 2,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.035 (140 hom., cov: 35)
  • Exomes 𝑓: 0.047 (1983 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026022792).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

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>A	p.Pro266His	missense	Exon 3 of 3	NP_113643.1	Q9BQI4-1
	CCDC3	NM_001282658.2		c.422C>A	p.Pro141His	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>A	p.Pro266His	missense	Exon 3 of 3	ENSP00000368102.3	Q9BQI4-1
	CCDC3	ENST00000870347.1		c.776C>A	p.Pro259His	missense	Exon 3 of 3	ENSP00000540406.1
	CCDC3	ENST00000378839.1	TSL:2	c.422C>A	p.Pro141His	missense	Exon 7 of 7	ENSP00000368116.1	Q9BQI4-2

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5400 AN: 152160 Hom.: 140 Cov.: 35

Gnomad AFR AF: 0.00890

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0360 AC: 8614 AN: 239566 AF XY: 0.0364

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.0847

Gnomad NFE exome AF: 0.0542

Gnomad OTH exome AF: 0.0329

GnomAD4 exome AF: 0.0471 AC: 68375 AN: 1451086 Hom.: 1983 Cov.: 48 AF XY: 0.0460 AC XY: 33104 AN XY: 720222

African (AFR) AF: 0.00702 AC: 232 AN: 33026

American (AMR) AF: 0.00995 AC: 438 AN: 44024

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 499 AN: 25898

East Asian (EAS) AF: 0.000253 AC: 10 AN: 39468

South Asian (SAS) AF: 0.00818 AC: 702 AN: 85836

European-Finnish (FIN) AF: 0.0796 AC: 4186 AN: 52580

Middle Eastern (MID) AF: 0.00439 AC: 22 AN: 5006

European-Non Finnish (NFE) AF: 0.0542 AC: 59957 AN: 1105464

Other (OTH) AF: 0.0390 AC: 2329 AN: 59784

GnomAD4 genome AF: 0.0354 AC: 5397 AN: 152278 Hom.: 140 Cov.: 35 AF XY: 0.0355 AC XY: 2640 AN XY: 74456

African (AFR) AF: 0.00888 AC: 369 AN: 41570

American (AMR) AF: 0.0137 AC: 210 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00974 AC: 47 AN: 4824

European-Finnish (FIN) AF: 0.0893 AC: 948 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3572 AN: 68002

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0219 Hom.: 20

Bravo AF: 0.0290

TwinsUK AF: 0.0456 AC: 169

ALSPAC AF: 0.0475 AC: 183

ESP6500AA AF: 0.00946 AC: 38

ESP6500EA AF: 0.0387 AC: 312

ExAC AF: 0.0363 AC: 4353

EpiCase AF: 0.0440

EpiControl AF: 0.0441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.078
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.32	B
Vest4		0.075
MPC		0.33
ClinPred		0.027	T
GERP RS		2.8
Varity_R		0.21
gMVP		0.19
Mutation Taster		=99/1	polymorphism (auto)

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: COSV106549963;