chr10-59812767-C-T

Variant names:

• chr10-59812767-C-T
• rs775541001
• NM_005436.5:c.715G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005436.5(CCDC6):​c.715G>A​(p.Val239Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,607,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V239A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1898104).
• BS2: High AC in GnomAdExome4 at 66 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC6	NM_005436.5	MANE Select	c.715G>A	p.Val239Ile	missense	Exon 5 of 9	NP_005427.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC6	ENST00000263102.7	TSL:1 MANE Select	c.715G>A	p.Val239Ile	missense	Exon 5 of 9	ENSP00000263102.6	Q16204
	CCDC6	ENST00000862752.1		c.715G>A	p.Val239Ile	missense	Exon 5 of 9	ENSP00000532811.1
	CCDC6	ENST00000936420.1		c.709G>A	p.Val237Ile	missense	Exon 5 of 9	ENSP00000606479.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000527 AC: 13 AN: 246854 AF XY: 0.0000600

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000801

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000453 AC: 66 AN: 1455652 Hom.: 0 Cov.: 28 AF XY: 0.0000539 AC XY: 39 AN XY: 723920

African (AFR) AF: 0.0000601 AC: 2 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39552

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84844

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000523 AC: 58 AN: 1108822

Other (OTH) AF: 0.0000333 AC: 2 AN: 60142

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

African (AFR) AF: 0.0000724 AC: 3 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000674 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.31
Sift	Benign	0.14	T
Sift4G	Benign	0.46	T
Polyphen		0.13	B
Vest4		0.48
MutPred		0.54		Gain of methylation at K234 (P = 0.0968)
MVP		0.45
MPC		1.0
ClinPred		0.14	T
GERP RS		5.7
Varity_R		0.067
gMVP		0.32
Mutation Taster		=76/24	polymorphism

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: rs775541001; hg19: chr10-61572525;