chr10-59794556-T-A

Position:

• chr10-59794556-T-A

Variant summary

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

The NM_005436.5(CCDC6):​c.1147A>T​(p.Thr383Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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]

CCDC6 (HGNC:):

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=0.17223135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC6	NM_005436.5	c.1147A>T	p.Thr383Ser	missense_variant	8/9	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7	c.1147A>T	p.Thr383Ser	missense_variant	8/9	1	NM_005436.5	ENSP00000263102.6
CCDC6	ENST00000491922.1	n.1199A>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 11, 2024

The c.1147A>T (p.T383S) alteration is located in exon 8 (coding exon 8) of the CCDC6 gene. This alteration results from a A to T substitution at nucleotide position 1147, causing the threonine (T) at amino acid position 383 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	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.078
Sift	Benign	0.58	T
Sift4G	Benign	1.0	T
Polyphen		0.015	B
Vest4		0.46
MutPred		0.055		Gain of phosphorylation at T380 (P = 0.0831);
MVP		0.30
MPC		0.26
ClinPred		0.51	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.22

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: chr10-61554314;