10-12962213-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC3	NM_031455.4	c.549+36125A>G		intron_variant	Intron 2 of 2	ENST00000378825.5	NP_113643.1
CCDC3	NM_001282658.2	c.174+36125A>G		intron_variant	Intron 6 of 6		NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378825.5	c.549+36125A>G		intron_variant	Intron 2 of 2	1	NM_031455.4	ENSP00000368102.3
CCDC3	ENST00000378839.1	c.174+36125A>G		intron_variant	Intron 6 of 6	2		ENSP00000368116.1
ENSG00000285520	ENST00000649832.1	n.1123-2239T>C		intron_variant	Intron 4 of 4

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.556

Alfa AF: 0.574 Hom.: 6438

Bravo AF: 0.500

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.25

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: rs10508451; hg19: chr10-13004213; COSMIC: COSV66561509;