NM_001141947.3:c.2825_2828dupAGAG

Variant names:

• chr3-56621593-A-AAGAG
• rs570037412
• NM_001141947.3:c.2825_2828dupAGAG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001141947.3(CCDC66):​c.2825_2828dupAGAG​(p.Ser943ArgfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,599,706 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0034 (9 hom.)
• Consequence: CCDC66 NM_001141947.3 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 3-56621593-A-AAGAG is Benign according to our data. Variant chr3-56621593-A-AAGAG is described in ClinVar as Likely_benign. ClinVar VariationId is 774299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	NM_001141947.3	MANE Select	c.2825_2828dupAGAG	p.Ser943ArgfsTer18	frameshift	Exon 18 of 18	NP_001135419.1	A2RUB6-1
	TASOR	NM_001365635.2	MANE Select	c.*1440_*1443dupCTCT		3_prime_UTR	Exon 24 of 24	NP_001352564.1	Q9UK61-1
	CCDC66	NM_001353147.1		c.2843_2846dupAGAG	p.Ser949ArgfsTer18	frameshift	Exon 18 of 18	NP_001340076.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.2825_2828dupAGAG	p.Ser943ArgfsTer18	frameshift	Exon 18 of 18	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.2723_2726dupAGAG	p.Ser909ArgfsTer18	frameshift	Exon 18 of 18	ENSP00000326050.7	A2RUB6-3
	TASOR	ENST00000683822.1	MANE Select	c.*1440_*1443dupCTCT		3_prime_UTR	Exon 24 of 24	ENSP00000508241.1	Q9UK61-1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00425

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00233 AC: 564 AN: 241740 AF XY: 0.00238

Gnomad AFR exome AF: 0.000561

Gnomad AMR exome AF: 0.000350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00209

Gnomad NFE exome AF: 0.00435

Gnomad OTH exome AF: 0.00136

GnomAD4 exome AF: 0.00342 AC: 4956 AN: 1447410 Hom.: 9 Cov.: 29 AF XY: 0.00342 AC XY: 2462 AN XY: 719994

African (AFR) AF: 0.000273 AC: 9 AN: 32972

American (AMR) AF: 0.000477 AC: 20 AN: 41894

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25748

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39380

South Asian (SAS) AF: 0.000240 AC: 20 AN: 83270

European-Finnish (FIN) AF: 0.00143 AC: 76 AN: 53038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00422 AC: 4668 AN: 1105666

Other (OTH) AF: 0.00270 AC: 161 AN: 59730

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152296 Hom.: 0 Cov.: 31 AF XY: 0.00205 AC XY: 153 AN XY: 74474

African (AFR) AF: 0.000866 AC: 36 AN: 41574

American (AMR) AF: 0.000915 AC: 14 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00425 AC: 289 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.00223

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=44/156	disease causing

Splicing

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

Other links and lift over

dbSNP: rs570037412; hg19: chr3-56655621; COSMIC: COSV100413618; COSMIC: COSV100413618;