NM_001141947.3:c.44A>G

Variant names:

• chr3-56558878-A-G
• rs748777335
• NM_001141947.3:c.44A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001141947.3(CCDC66):​c.44A>G​(p.Asp15Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC66 NM_001141947.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.44A>G	p.Asp15Gly	missense_variant	Exon 2 of 18	ENST00000394672.8	NP_001135419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8	c.44A>G	p.Asp15Gly	missense_variant	Exon 2 of 18	1	NM_001141947.3	ENSP00000378167.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.99	.;D
Vest4		0.44
MutPred		0.25		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.74
MPC		0.11
ClinPred		0.99	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs748777335; hg19: chr3-56592906;