rs895364091

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-59906388-C-A
• chr10-59906388-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC6	NM_005436.5	c.37G>T	p.Ala13Ser	missense_variant	Exon 1 of 9	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7	c.37G>T	p.Ala13Ser	missense_variant	Exon 1 of 9	1	NM_005436.5	ENSP00000263102.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000481 AC: 1 AN: 207860 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116440

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R		0.17
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs895364091; hg19: chr10-61666146;