10-59906388-C-A

Variant names:

• chr10-59906388-C-A
• rs895364091
• NM_005436.5:c.37G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005436.5(CCDC6):​c.37G>T​(p.Ala13Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A13T) 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: 4.83
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3428505).

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.37G>T	p.Ala13Ser	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.37G>T	p.Ala13Ser	missense	Exon 1 of 9	ENSP00000263102.6	Q16204
	CCDC6	ENST00000862752.1		c.37G>T	p.Ala13Ser	missense	Exon 1 of 9	ENSP00000532811.1
	CCDC6	ENST00000936420.1		c.37G>T	p.Ala13Ser	missense	Exon 1 of 9	ENSP00000606479.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000481 AC: 1 AN: 207860 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433666 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 712946

African (AFR) AF: 0.00 AC: 0 AN: 32294

American (AMR) AF: 0.0000229 AC: 1 AN: 43650

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 38946

South Asian (SAS) AF: 0.00 AC: 0 AN: 84830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106480

Other (OTH) AF: 0.00 AC: 0 AN: 59510

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	0.69	N
PhyloP100		4.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.010	N
REVEL	Uncertain	0.41
Sift	Benign	0.42	T
Sift4G	Benign	0.43	T
Polyphen		0.80	P
Vest4		0.30
MutPred		0.32		Gain of phosphorylation at A13 (P = 0.0011)
MVP		0.78
MPC		1.3
ClinPred		0.66	D
GERP RS		4.3
PromoterAI		0.024	Neutral
Varity_R		0.17
gMVP		0.67
Mutation Taster		=45/55	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: rs895364091; hg19: chr10-61666146;