3-56621584-A-G

Variant names:

• chr3-56621584-A-G
• NM_001141947.3:c.2813A>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.2813A>G​(p.Glu938Gly) 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. 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: 31)
• Consequence: CCDC66 NM_001141947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.802

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]

TASOR (HGNC:30314): (transcription activation suppressor) Enables chromatin binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; protein localization to heterochromatin; and regulation of gene expression. Located in heterochromatin and nucleoplasm. [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=0.08044362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.2813A>G	p.Glu938Gly	missense_variant	Exon 18 of 18	ENST00000394672.8	NP_001135419.1
TASOR	NM_001365635.2	c.*1453T>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000683822.1	NP_001352564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8	c.2813A>G	p.Glu938Gly	missense_variant	Exon 18 of 18	1	NM_001141947.3	ENSP00000378167.3
TASOR	ENST00000683822	c.*1453T>C		3_prime_UTR_variant	Exon 24 of 24		NM_001365635.2	ENSP00000508241.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2813A>G (p.E938G) alteration is located in exon 18 (coding exon 18) of the CCDC66 gene. This alteration results from a A to G substitution at nucleotide position 2813, causing the glutamic acid (E) at amino acid position 938 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	0.073
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.042	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.12
Sift	Benign	0.19	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0080	B;.
Vest4		0.15
MutPred		0.052		Gain of loop (P = 0.0166);.;
MVP		0.31
MPC		0.018
ClinPred		0.081	T
GERP RS		3.5
Varity_R		0.037
gMVP		0.095

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-56655612;