Genetic Variant NM_001141947.3:c.11+7_11+16delAGGGGTAAGC (chr3-56557250-TGGGGTAAGCA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001141947.3(CCDC66):c.11+7_11+16delAGGGGTAAGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,546,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CCDC66
NM_001141947.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.42

Publications

3 publications found

Variant links:

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]

CCDC66 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC66	NM_001141947.3	MANE Select	c.11+7_11+16delAGGGGTAAGC	splice_region intron	N/A	NP_001135419.1
CCDC66	NM_001353153.1		c.-95_-92+6delAGGGGTAAGC	splice_region	Exon 1 of 18	NP_001340082.1
CCDC66	NM_001353160.1		c.-1248_-1245+6delAGGGGTAAGC	splice_region	Exon 1 of 19	NP_001340089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.9_11+7delGGGGTAAGCA	p.Gly4del	splice_donor disruptive_inframe_deletion splice_region intron	Exon 1 of 18	ENSP00000378167.3
CCDC66	ENST00000326595.11	TSL:1	c.-92+17_-92+26delGGGGTAAGCA		intron	N/A	ENSP00000326050.7
CCDC66	ENST00000341455.10	TSL:1	n.9_11+7delGGGGTAAGCA		splice_donor splice_region intron non_coding_transcript_exon	Exon 1 of 18	ENSP00000343840.6

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000963

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1396516

Hom.:

AF XY:

0.0000145

AC XY:

AN XY:

688726

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31554

American (AMR)

AF:

0.00

AC:

AN:

35640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35704

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79180

European-Finnish (FIN)

AF:

0.0000615

AC:

AN:

48776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000929

AC:

AN:

1076896

Other (OTH)

AF:

0.0000518

AC:

AN:

57938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150448

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40862

American (AMR)

AF:

0.00

AC:

AN:

15120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

4998

South Asian (SAS)

AF:

0.00

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.0000963

AC:

AN:

10386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67634

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

4713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over