10-59906385-C-T

Variant names:

• chr10-59906385-C-T
• rs762472389
• NM_005436.5:c.40G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005436.5(CCDC6):​c.40G>A​(p.Gly14Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,674 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G14W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.40G>A	p.Gly14Arg	missense	Exon 1 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.40G>A	p.Gly14Arg	missense	Exon 1 of 9	ENSP00000263102.6	Q16204
	CCDC6	ENST00000862752.1		c.40G>A	p.Gly14Arg	missense	Exon 1 of 9	ENSP00000532811.1
	CCDC6	ENST00000936420.1		c.40G>A	p.Gly14Arg	missense	Exon 1 of 9	ENSP00000606479.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433674 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 712984

African (AFR) AF: 0.00 AC: 0 AN: 32284

American (AMR) AF: 0.00 AC: 0 AN: 43642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25558

East Asian (EAS) AF: 0.00 AC: 0 AN: 38932

South Asian (SAS) AF: 0.00 AC: 0 AN: 84860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106470

Other (OTH) AF: 0.0000168 AC: 1 AN: 59528

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Benign	0.90	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.32	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.41		Gain of methylation at G14 (P = 0.0537)
MVP		0.58
MPC		1.5
ClinPred		0.98	D
GERP RS		4.3
PromoterAI		0.065	Neutral
Varity_R		0.24
gMVP		0.64
Mutation Taster		=39/61	disease causing

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: rs762472389; hg19: chr10-61666143;