chr10-59792934-G-T

Variant names:

• chr10-59792934-G-T
• rs1053266
• NM_005436.5:c.1408C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005436.5(CCDC6):​c.1408C>A​(p.Pro470Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,609,104 control chromosomes in the GnomAD database, including 202,591 homozygotes. 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: 𝑓 0.44 (15707 hom., cov: 33)
  • Exomes 𝑓: 0.50 (186884 hom.)
• Consequence: CCDC6 NM_005436.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• Publications: 47 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.9169785E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC6	NM_005436.5	MANE Select	c.1408C>A	p.Pro470Thr	missense	Exon 9 of 9	NP_005427.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC6	ENST00000263102.7	TSL:1 MANE Select	c.1408C>A	p.Pro470Thr	missense	Exon 9 of 9	ENSP00000263102.6
	CCDC6	ENST00000491922.1	TSL:2	n.1460C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66756 AN: 151932 Hom.: 15693 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.460

GnomAD2 exomes AF: 0.511 AC: 126490 AN: 247466 AF XY: 0.511

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.503 AC: 733356 AN: 1457052 Hom.: 186884 Cov.: 47 AF XY: 0.504 AC XY: 364974 AN XY: 724300

African (AFR) AF: 0.256 AC: 8549 AN: 33412

American (AMR) AF: 0.636 AC: 28278 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11661 AN: 25706

East Asian (EAS) AF: 0.578 AC: 22912 AN: 39672

South Asian (SAS) AF: 0.496 AC: 42350 AN: 85356

European-Finnish (FIN) AF: 0.474 AC: 25198 AN: 53146

Middle Eastern (MID) AF: 0.506 AC: 2897 AN: 5722

European-Non Finnish (NFE) AF: 0.506 AC: 561541 AN: 1109336

Other (OTH) AF: 0.498 AC: 29970 AN: 60212

GnomAD4 genome AF: 0.439 AC: 66782 AN: 152052 Hom.: 15707 Cov.: 33 AF XY: 0.441 AC XY: 32796 AN XY: 74304

African (AFR) AF: 0.261 AC: 10827 AN: 41472

American (AMR) AF: 0.532 AC: 8127 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3151 AN: 5172

South Asian (SAS) AF: 0.483 AC: 2324 AN: 4812

European-Finnish (FIN) AF: 0.472 AC: 4981 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34242 AN: 67964

Other (OTH) AF: 0.461 AC: 976 AN: 2116

Alfa AF: 0.471 Hom.: 36111

Bravo AF: 0.440

TwinsUK AF: 0.505 AC: 1874

ALSPAC AF: 0.502 AC: 1935

ESP6500AA AF: 0.264 AC: 1164

ESP6500EA AF: 0.503 AC: 4329

ExAC AF: 0.500 AC: 60692

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.000089	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.81	L
PhyloP100		8.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.16
MPC		0.32
ClinPred		0.050	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.18
Mutation Taster		=77/23	polymorphism (auto)

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: rs1053266; hg19: chr10-61552692; COSMIC: COSV54054295;