3-56563853-C-A

Variant names:

• chr3-56563853-C-A
• rs2065443703
• NM_001141947.3:c.272C>A

Variant summary

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

The NM_001141947.3(CCDC66):​c.272C>A​(p.Ser91Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC66 NM_001141947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• Publications: 0 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: 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=0.2906207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141947.3. 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.272C>A	p.Ser91Tyr	missense	Exon 4 of 18	NP_001135419.1	A2RUB6-1
	CCDC66	NM_001353147.1		c.272C>A	p.Ser91Tyr	missense	Exon 4 of 18	NP_001340076.1
	CCDC66	NM_001353148.1		c.272C>A	p.Ser91Tyr	missense	Exon 4 of 18	NP_001340077.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.272C>A	p.Ser91Tyr	missense	Exon 4 of 18	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.170C>A	p.Ser57Tyr	missense	Exon 4 of 18	ENSP00000326050.7	A2RUB6-3
	CCDC66	ENST00000341455.10	TSL:1	n.272C>A		non_coding_transcript_exon	Exon 4 of 18	ENSP00000343840.6	F8WCY0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.29	T
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.36
Sift	Benign	0.092	T
Sift4G	Uncertain	0.058	T
Polyphen		0.94	P
Vest4		0.20
MVP		0.61
MPC		0.039
ClinPred		0.57	D
GERP RS		4.9
Varity_R		0.099
gMVP		0.068
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2065443703; hg19: chr3-56597881;