10-59906331-C-T

Position:

• chr10-59906331-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005436.5(CCDC6):​c.94G>A​(p.Gly32Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC6	NM_005436.5	c.94G>A	p.Gly32Ser	missense_variant	1/9	ENST00000263102.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC6	ENST00000263102.7	c.94G>A	p.Gly32Ser	missense_variant	1/9	1	NM_005436.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.94G>A (p.G32S) alteration is located in exon 1 (coding exon 1) of the CCDC6 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the glycine (G) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.98	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.24	N
REVEL	Uncertain	0.39
Sift	Benign	0.43	T
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.35		Gain of phosphorylation at G32 (P = 0.0037);
MVP		0.68
MPC		1.3
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.21
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-61666089;