NM_005436.5:c.94G>A

Variant names:

• chr10-59906331-C-T
• NM_005436.5:c.94G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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.94G>A	p.Gly32Ser	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.94G>A	p.Gly32Ser	missense	Exon 1 of 9	ENSP00000263102.6	Q16204
	CCDC6	ENST00000862752.1		c.94G>A	p.Gly32Ser	missense	Exon 1 of 9	ENSP00000532811.1
	CCDC6	ENST00000936420.1		c.94G>A	p.Gly32Ser	missense	Exon 1 of 9	ENSP00000606479.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.086
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
PhyloP100		4.6
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
PromoterAI		-0.015	Neutral
Varity_R		0.21
gMVP		0.71
Mutation Taster		=84/16	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

hg19: chr10-61666089;