Variant 12-48918910-CAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_033124.5(CCDC65):c.1026+8_1026+9delAG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,604,740 control chromosomes in the GnomAD database, including 9,147 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 942 hom., cov: 30)

Exomes 𝑓: 0.087 ( 8205 hom. )

Consequence

CCDC65
NM_033124.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

CCDC65 (HGNC:29937): (coiled-coil domain containing 65) This gene encodes a sperm tail protein that is highly expressed in adult testis, spermatocytes and spermatids. The protein plays a critical role in the assembly of the nexin-dynein regulatory complex. Mutations in this gene result in primary ciliary dyskinesia. [provided by RefSeq, Nov 2013]

CCDC65 links:

ENSG00000272822 (HGNC:):

ENSG00000272822 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-48918910-CAG-C is Benign according to our data. Variant chr12-48918910-CAG-C is described in ClinVar as [Benign]. Clinvar id is 220953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC65	NM_033124.5 linkuse as main transcript	c.1026+8_1026+9delAG		splice_region_variant, intron_variant		ENST00000320516.5	NP_149115.2	Q8IXS2-1
CCDC65	NM_001286957.2 linkuse as main transcript	c.597+8_597+9delAG		splice_region_variant, intron_variant			NP_001273886.1	B4DXQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 linkuse as main transcript	c.1026+8_1026+9delAG		splice_region_variant, intron_variant		1	NM_033124.5	ENSP00000312706.4		Q8IXS2-1
ENSG00000272822	ENST00000398092.4 linkuse as main transcript	c.385-15004_385-15003delCT		intron_variant		3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.0813

AC:

12364

AN:

152014

Hom.:

931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.0806

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0707

Gnomad OTH

AF:

0.0852

GnomAD3 exomes

AF:

0.126

AC:

31677

AN:

250664

Hom.:

3464

AF XY:

0.117

AC XY:

15805

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.0748

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0759

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0872

AC:

126608

AN:

1452608

Hom.:

8205

AF XY:

0.0860

AC XY:

62193

AN XY:

723196

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.0497

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.0754

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.0823

GnomAD4 genome

AF:

0.0814

AC:

12391

AN:

152132

Hom.:

942

Cov.:

AF XY:

0.0868

AC XY:

6456

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.0424

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.0809

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.0707

Gnomad4 OTH

AF:

0.0914

Alfa

AF:

0.0705

Hom.:

Bravo

AF:

0.0915

Asia WGS

AF:

0.182

AC:

632

AN:

3478

EpiCase

AF:

0.0721

EpiControl

AF:

0.0729

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Frequency -

Primary ciliary dyskinesia 27

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over