3-56563853-C-A

Position:

• chr3-56563853-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2906207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC66	NM_001141947.3	c.272C>A	p.Ser91Tyr	missense_variant	4/18	ENST00000394672.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC66	ENST00000394672.8	c.272C>A	p.Ser91Tyr	missense_variant	4/18	1	NM_001141947.3	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.272C>A (p.S91Y) alteration is located in exon 4 (coding exon 4) of the CCDC66 gene. This alteration results from a C to A substitution at nucleotide position 272, causing the serine (S) at amino acid position 91 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	0.90	.;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.092	T;D;D
Sift4G	Uncertain	0.058	T;T;T
Polyphen		0.94	.;P;.
Vest4		0.20, 0.20
MVP		0.61
MPC		0.039
ClinPred		0.57	D
GERP RS		4.9
Varity_R		0.099
gMVP		0.068

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-56597881;