rs548084281

Variant names:

• chr3-56558908-A-G
• rs548084281
• ENST00000326595.11:c.-29A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-56558908-A-G
• chr3-56558908-A-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001012506.5(CCDC66):​c.-29A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000094 in 1,542,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: CCDC66 NM_001012506.5 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.007349
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0980
• Publications: 1 publications found

Genes affected

CCDC66 (HGNC:27709): (coiled-coil domain containing 66) Enables microtubule binding activity. Involved in cilium assembly; microtubule bundle formation; and regulation of protein localization to cilium. Located in several cellular components, including Flemming body; microtubule cytoskeleton; and photoreceptor inner segment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01966986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012506.5. 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
	CCDC66	NM_001141947.3	MANE Select	c.74A>G	p.Tyr25Cys	missense splice_region	Exon 2 of 18	NP_001135419.1	A2RUB6-1
	CCDC66	NM_001012506.5		c.-29A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	NP_001012524.4	A2RUB6-3
	CCDC66	NM_001353152.1		c.-180A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_001340081.1	A2RUB6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	ENST00000326595.11	TSL:1	c.-29A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	ENSP00000326050.7	A2RUB6-3
	CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.74A>G	p.Tyr25Cys	missense splice_region	Exon 2 of 18	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.-29A>G		splice_region	Exon 2 of 18	ENSP00000326050.7	A2RUB6-3

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000902 AC: 14 AN: 155290 AF XY: 0.0000609

Gnomad AFR exome AF: 0.00176

Gnomad AMR exome AF: 0.00

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: 0.0000597 AC: 83 AN: 1390522 Hom.: 0 Cov.: 27 AF XY: 0.0000495 AC XY: 34 AN XY: 686218

African (AFR) AF: 0.000828 AC: 26 AN: 31388

American (AMR) AF: 0.0000283 AC: 1 AN: 35376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25060

East Asian (EAS) AF: 0.00 AC: 0 AN: 35528

South Asian (SAS) AF: 0.0000255 AC: 2 AN: 78478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48996

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5612

European-Non Finnish (NFE) AF: 0.0000476 AC: 51 AN: 1072416

Other (OTH) AF: 0.0000347 AC: 2 AN: 57668

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74492

African (AFR) AF: 0.00144 AC: 60 AN: 41596

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000839 Hom.: 0

Bravo AF: 0.000393

ExAC AF: 0.000122 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.020	T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Benign	1.4	L
PhyloP100		-0.098
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.40
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.023	B
Vest4		0.27
MVP		0.59
MPC		0.11
ClinPred		0.081	T
GERP RS		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.075
gMVP		0.22
Mutation Taster		=269/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0073
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.030		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: rs548084281; hg19: chr3-56592936;