3-56563961-C-A

Variant names:

• chr3-56563961-C-A
• NM_001141947.3:c.380C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001141947.3(CCDC66):​c.380C>A​(p.Thr127Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC66 NM_001141947.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060156494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.380C>A	p.Thr127Lys	missense_variant	Exon 4 of 18	ENST00000394672.8	NP_001135419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8	c.380C>A	p.Thr127Lys	missense_variant	Exon 4 of 18	1	NM_001141947.3	ENSP00000378167.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461608 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.16
DEOGEN2	Benign	0.0046	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.54	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	.;B;.
Vest4		0.069, 0.066
MutPred		0.23		Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);.;
MVP		0.085
MPC		0.017
ClinPred		0.14	T
GERP RS		-0.52
Varity_R		0.034
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-56597989;