10-12962213-T-C

Variant names:

• chr10-12962213-T-C
• rs10508451
• NM_031455.4:c.549+36125A>G

Variant summary

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

The NM_031455.4(CCDC3):​c.549+36125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,078 control chromosomes in the GnomAD database, including 23,092 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 0.52 (23092 hom., cov: 33)
• Consequence: CCDC3 NM_031455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 4 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	NM_031455.4	MANE Select	c.549+36125A>G		intron	N/A	NP_113643.1
	CCDC3	NM_001282658.2		c.174+36125A>G		intron	N/A	NP_001269587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	ENST00000378825.5	TSL:1 MANE Select	c.549+36125A>G		intron	N/A	ENSP00000368102.3
	CCDC3	ENST00000378839.1	TSL:2	c.174+36125A>G		intron	N/A	ENSP00000368116.1
	ENSG00000285520	ENST00000649832.1		n.1123-2239T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79256 AN: 151960 Hom.: 23098 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.521 AC: 79258 AN: 152078 Hom.: 23092 Cov.: 33 AF XY: 0.519 AC XY: 38605 AN XY: 74352

African (AFR) AF: 0.245 AC: 10166 AN: 41474

American (AMR) AF: 0.509 AC: 7776 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2426 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2995 AN: 5170

South Asian (SAS) AF: 0.515 AC: 2483 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6829 AN: 10584

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44513 AN: 67982

Other (OTH) AF: 0.556 AC: 1172 AN: 2108

Alfa AF: 0.578 Hom.: 14775

Bravo AF: 0.500

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.25
PhyloP100		-0.61
Mutation Taster		=100/0	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: rs10508451; hg19: chr10-13004213; COSMIC: COSV66561509;