10-59821209-A-G

Variant names:

• chr10-59821209-A-G
• rs920964
• NM_005436.5:c.583-6454T>C

Variant summary

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

The NM_005436.5(CCDC6):​c.583-6454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,336 control chromosomes in the GnomAD database, including 70,193 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 0.96 (70193 hom., cov: 32)
• Consequence: CCDC6 NM_005436.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 2 publications found

Genes affected

CCDC6 (HGNC:18782): (coiled-coil domain containing 6) This gene encodes a coiled-coil domain-containing protein. The encoded protein is ubiquitously expressed and may function as a tumor suppressor. A chromosomal rearrangement resulting in the expression of a fusion gene containing a portion of this gene and the intracellular kinase-encoding domain of the ret proto-oncogene is the cause of thyroid papillary carcinoma.[provided by RefSeq, Sep 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005436.5. 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
	CCDC6	NM_005436.5	MANE Select	c.583-6454T>C		intron	N/A	NP_005427.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC6	ENST00000263102.7	TSL:1 MANE Select	c.583-6454T>C		intron	N/A	ENSP00000263102.6

Frequencies

GnomAD3 genomes AF: 0.959 AC: 146046 AN: 152218 Hom.: 70130 Cov.: 32

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.960 AC: 146168 AN: 152336 Hom.: 70193 Cov.: 32 AF XY: 0.961 AC XY: 71589 AN XY: 74492

African (AFR) AF: 0.989 AC: 41114 AN: 41576

American (AMR) AF: 0.967 AC: 14793 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3316 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5188

South Asian (SAS) AF: 0.994 AC: 4803 AN: 4830

European-Finnish (FIN) AF: 0.942 AC: 9995 AN: 10616

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63752 AN: 68038

Other (OTH) AF: 0.963 AC: 2037 AN: 2116

Alfa AF: 0.945 Hom.: 45155

Bravo AF: 0.963

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.59
PhyloP100		-0.86
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: rs920964; hg19: chr10-61580967;