10-13099144-C-T

Variant names:

• chr10-13099144-C-T
• rs3829923
• NM_001282658.2:c.-641G>A

Variant summary

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

The NM_001282658.2(CCDC3):​c.-641G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,096 control chromosomes in the GnomAD database, including 7,266 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 0.28 (7252 hom., cov: 29)
  • Exomes 𝑓: 0.38 (14 hom.)
• Consequence: CCDC3 NM_001282658.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282658.2. 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
	CCDC3	NM_001282658.2		c.-641G>A		5_prime_UTR	Exon 2 of 7	NP_001269587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	ENST00000378839.1	TSL:2	c.-641G>A		5_prime_UTR	Exon 2 of 7	ENSP00000368116.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41825 AN: 151816 Hom.: 7248 Cov.: 29

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.383 AC: 62 AN: 162 Hom.: 14 Cov.: 0 AF XY: 0.395 AC XY: 49 AN XY: 124

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.412 AC: 56 AN: 136

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.275 AC: 41826 AN: 151934 Hom.: 7252 Cov.: 29 AF XY: 0.278 AC XY: 20624 AN XY: 74252

African (AFR) AF: 0.0774 AC: 3212 AN: 41498

American (AMR) AF: 0.206 AC: 3152 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1690 AN: 5146

South Asian (SAS) AF: 0.356 AC: 1712 AN: 4804

European-Finnish (FIN) AF: 0.430 AC: 4533 AN: 10538

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25265 AN: 67910

Other (OTH) AF: 0.255 AC: 535 AN: 2094

Alfa AF: 0.320 Hom.: 10869

Bravo AF: 0.247

Asia WGS AF: 0.308 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-2.7
PromoterAI		-0.033	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3829923; hg19: chr10-13141144; COSMIC: COSV53811399; COSMIC: COSV53811399;