3-56563846-T-C

Variant names:

• chr3-56563846-T-C
• NM_001141947.3:c.265T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001141947.3(CCDC66):​c.265T>C​(p.Phe89Leu) 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: -0.0820
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08258909).

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.265T>C	p.Phe89Leu	missense	Exon 4 of 18	NP_001135419.1	A2RUB6-1
	CCDC66	NM_001353147.1		c.265T>C	p.Phe89Leu	missense	Exon 4 of 18	NP_001340076.1
	CCDC66	NM_001353148.1		c.265T>C	p.Phe89Leu	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.265T>C	p.Phe89Leu	missense	Exon 4 of 18	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.163T>C	p.Phe55Leu	missense	Exon 4 of 18	ENSP00000326050.7	A2RUB6-3
	CCDC66	ENST00000341455.10	TSL:1	n.265T>C		non_coding_transcript_exon	Exon 4 of 18	ENSP00000343840.6	F8WCY0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.82
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.083	T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	1.7	L
PhyloP100		-0.082
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Benign	0.76	T
Sift4G	Benign	0.87	T
Polyphen		0.0090	B
Vest4		0.073
MutPred		0.19		Loss of catalytic residue at F89 (P = 0.0408)
MVP		0.44
MPC		0.017
ClinPred		0.031	T
GERP RS		0.66
Varity_R		0.092
gMVP		0.046
Mutation Taster		=96/4	polymorphism

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

hg19: chr3-56597874;