rs117646559

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033124.5(CCDC65):c.1021G>T(p.Asp341Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,610,524 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 7 hom., cov: 31)

Exomes 𝑓: 0.012 ( 117 hom. )

Consequence

CCDC65
NM_033124.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.610

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040610135).

BP6

Variant 12-48918898-G-T is Benign according to our data. Variant chr12-48918898-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 416603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-48918898-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00814 (1224/150326) while in subpopulation NFE AF= 0.0125 (844/67702). AF 95% confidence interval is 0.0118. There are 7 homozygotes in gnomad4. There are 580 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC65	NM_033124.5 link	c.1021G>T	p.Asp341Tyr	missense_variant	Exon 6 of 8	ENST00000320516.5	NP_149115.2	Q8IXS2-1
CCDC65	NM_001286957.2 link	c.592G>T	p.Asp198Tyr	missense_variant	Exon 6 of 8		NP_001273886.1	B4DXQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 link	c.1021G>T	p.Asp341Tyr	missense_variant	Exon 6 of 8	1	NM_033124.5	ENSP00000312706.4		Q8IXS2-1
ENSG00000272822	ENST00000398092.4 link	c.385-14990C>A		intron_variant	Intron 4 of 4	3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.00815

AC:

1225

AN:

150226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.00293

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000205

Gnomad SAS

AF:

0.00631

Gnomad FIN

AF:

0.00508

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00870

GnomAD3 exomes

AF:

0.00752

AC:

1887

AN:

251054

Hom.:

AF XY:

0.00780

AC XY:

1058

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00750

GnomAD4 exome

AF:

0.0117

AC:

17033

AN:

1460198

Hom.:

117

Cov.:

AF XY:

0.0115

AC XY:

8355

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00653

Gnomad4 FIN exome

AF:

0.00509

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.00936

GnomAD4 genome

AF:

0.00814

AC:

1224

AN:

150326

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

580

AN XY:

73372

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.00292

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.000206

Gnomad4 SAS

AF:

0.00632

Gnomad4 FIN

AF:

0.00508

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00866

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00798

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0149

AC:

128

ExAC

AF:

0.00732

AC:

889

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 27

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 04, 2024

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CCDC65: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;.;T

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.065

Sift

Uncertain

0.020

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.95

.;.;P

Vest4

0.38

MVP

0.048

MPC

0.24

ClinPred

0.017

GERP RS

3.8

Varity_R

0.34

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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