rs10875894

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033124.5(CCDC65):c.1176C>A(p.Thr392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,902 control chromosomes in the GnomAD database, including 114,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9119 hom., cov: 31)

Exomes 𝑓: 0.37 ( 105828 hom. )

Consequence

CCDC65
NM_033124.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0960

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-48921079-C-A is Benign according to our data. Variant chr12-48921079-C-A is described in ClinVar as [Benign]. Clinvar id is 402503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.096 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5 linkuse as main transcript	c.1176C>A	p.Thr392=	synonymous_variant	7/8	ENST00000320516.5
CCDC65	NM_001286957.2 linkuse as main transcript	c.747C>A	p.Thr249=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5 linkuse as main transcript	c.1176C>A	p.Thr392=	synonymous_variant	7/8	1	NM_033124.5	P2	Q8IXS2-1
CCDC65	ENST00000266984.9 linkuse as main transcript	c.1176C>A	p.Thr392=	synonymous_variant	7/9	5		A2	Q8IXS2-2
CCDC65	ENST00000552942.5 linkuse as main transcript	c.867C>A	p.Thr289=	synonymous_variant	5/6	5
CCDC65	ENST00000547861.5 linkuse as main transcript	c.*1007C>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49549

AN:

151890

Hom.:

9111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.382

AC:

95332

AN:

249870

Hom.:

19790

AF XY:

0.373

AC XY:

50460

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.466

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.375

AC:

546543

AN:

1457894

Hom.:

105828

Cov.:

AF XY:

0.371

AC XY:

269081

AN XY:

724668

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.326

AC:

49568

AN:

152008

Hom.:

9119

Cov.:

AF XY:

0.330

AC XY:

24508

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.380

Hom.:

14474

Bravo

AF:

0.337

Asia WGS

AF:

0.358

AC:

1242

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 27

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.78

Dann

Benign

0.68

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