chr3-56563889-A-G

Variant names:

• chr3-56563889-A-G
• NM_001141947.3:c.308A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001141947.3(CCDC66):​c.308A>G​(p.Asp103Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 4.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07437503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.308A>G	p.Asp103Gly	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.308A>G	p.Asp103Gly	missense_variant	Exon 4 of 18	1	NM_001141947.3	ENSP00000378167.3

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

Jul 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308A>G (p.D103G) alteration is located in exon 4 (coding exon 4) of the CCDC66 gene. This alteration results from a A to G substitution at nucleotide position 308, causing the aspartic acid (D) at amino acid position 103 to be replaced by a glycine (G). 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	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.099	.;B;.
Vest4		0.21, 0.22
MutPred		0.36		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;
MVP		0.22
MPC		0.025
ClinPred		0.24	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-56597917;