10-12896961-C-T

Position:

• chr10-12896961-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031455.4(CCDC3):​c.*1455G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,258 control chromosomes in the GnomAD database, including 4,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4238 hom., cov: 32)
  • Exomes 𝑓: 0.32 (11 hom.)
• Consequence: CCDC3 NM_031455.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC3	NM_031455.4	c.*1455G>A		3_prime_UTR_variant	3/3	ENST00000378825.5
CCDC3	NM_001282658.2	c.*1455G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC3	ENST00000378825.5	c.*1455G>A		3_prime_UTR_variant	3/3	1	NM_031455.4	P1
	ENST00000649832.1	n.511-1551C>T		intron_variant, non_coding_transcript_variant
CCDC3	ENST00000378839.1	c.*1455G>A		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32362 AN: 151964 Hom.: 4242 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.324 AC: 57 AN: 176 Hom.: 11 Cov.: 0 AF XY: 0.319 AC XY: 46 AN XY: 144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.213 AC: 32346 AN: 152082 Hom.: 4238 Cov.: 32 AF XY: 0.210 AC XY: 15587 AN XY: 74330

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.222

Alfa AF: 0.279 Hom.: 8427

Bravo AF: 0.204

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280076; hg19: chr10-12938961;