10-12898429-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031455.4(CCDC3):c.799del(p.Tyr267ThrfsTer21) variant causes a frameshift change. The variant allele was found at a frequency of 0.000638 in 1,603,052 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00094 (2 hom., cov: 35)
  • Exomes 𝑓: 0.00061 (11 hom.)
• Consequence: CCDC3 NM_031455.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.02

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 -10 ACMG points.

• BP6: Variant 10-12898429-TA-T is Benign according to our data. Variant chr10-12898429-TA-T is described in ClinVar as [Benign]. Clinvar id is 786779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000607 (880/1450790) while in subpopulation AMR AF= 0.0192 (846/43962). AF 95% confidence interval is 0.0182. There are 11 homozygotes in gnomad4_exome. There are 370 alleles in male gnomad4_exome subpopulation. Median coverage is 44. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC3	NM_031455.4	c.799del	p.Tyr267ThrfsTer21	frameshift_variant	3/3	ENST00000378825.5
CCDC3	NM_001282658.2	c.424del	p.Tyr142ThrfsTer21	frameshift_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC3	ENST00000378825.5	c.799del	p.Tyr267ThrfsTer21	frameshift_variant	3/3	1	NM_031455.4	P1
	ENST00000649832.1	n.511-82del		intron_variant, non_coding_transcript_variant
CCDC3	ENST00000378839.1	c.424del	p.Tyr142ThrfsTer21	frameshift_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.000927 AC: 141 AN: 152144 Hom.: 2 Cov.: 35

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00315 AC: 755 AN: 239570 Hom.: 10 AF XY: 0.00231 AC XY: 304 AN XY: 131446

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.0219

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000935

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.000607 AC: 880 AN: 1450790 Hom.: 11 Cov.: 44 AF XY: 0.000514 AC XY: 370 AN XY: 720110

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000905

Gnomad4 OTH exome AF: 0.000335

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152262 Hom.: 2 Cov.: 35 AF XY: 0.00105 AC XY: 78 AN XY: 74462

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000870 Hom.: 0

Bravo AF: 0.00190

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs556171792; hg19: chr10-12940429; COSMIC: COSV66559967;