chr10-59812682-T-C

Variant names:

• chr10-59812682-T-C
• NM_005436.5:c.800A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005436.5(CCDC6):​c.800A>G​(p.Asn267Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15427706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC6	NM_005436.5	c.800A>G	p.Asn267Ser	missense_variant	Exon 5 of 9	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7	c.800A>G	p.Asn267Ser	missense_variant	Exon 5 of 9	1	NM_005436.5	ENSP00000263102.6
CCDC6	ENST00000518638.1	n.47A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.800A>G (p.N267S) alteration is located in exon 5 (coding exon 5) of the CCDC6 gene. This alteration results from a A to G substitution at nucleotide position 800, causing the asparagine (N) at amino acid position 267 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	0.082
BayesDel_addAF	Benign	-0.00082	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.62	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.29	N
REVEL	Uncertain	0.35
Sift	Benign	0.91	T
Sift4G	Benign	0.85	T
Polyphen		0.0050	B
Vest4		0.24
MutPred		0.31		Gain of phosphorylation at N267 (P = 0.0707);
MVP		0.46
MPC		0.96
ClinPred		0.65	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.20

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: chr10-61572440;