rs4760600

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033124.5(CCDC65):c.1223A>G(p.Tyr408Cys) variant causes a missense change. The variant allele was found at a frequency of 0.37 in 1,613,700 control chromosomes in the GnomAD database, including 115,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9105 hom., cov: 31)

Exomes 𝑓: 0.37 ( 106109 hom. )

Consequence

CCDC65
NM_033124.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.97

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=0.0031661987).

BP6

Variant 12-48921211-A-G is Benign according to our data. Variant chr12-48921211-A-G is described in ClinVar as [Benign]. Clinvar id is 402504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CCDC65	NM_033124.5 link	c.1223A>G	p.Tyr408Cys	missense_variant	Exon 8 of 8	ENST00000320516.5	NP_149115.2	Q8IXS2-1
CCDC65	NM_001286957.2 link	c.794A>G	p.Tyr265Cys	missense_variant	Exon 8 of 8		NP_001273886.1	B4DXQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 link	c.1223A>G	p.Tyr408Cys	missense_variant	Exon 8 of 8	1	NM_033124.5	ENSP00000312706.4		Q8IXS2-1
ENSG00000272822	ENST00000398092.4 link	c.385-17303T>C		intron_variant	Intron 4 of 4	3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49528

AN:

151948

Hom.:

9098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.465

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:

95798

AN:

251020

Hom.:

19885

AF XY:

0.373

AC XY:

50646

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.438

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:

547957

AN:

1461636

Hom.:

106109

Cov.:

AF XY:

0.371

AC XY:

270029

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.474

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:

49545

AN:

152064

Hom.:

9105

Cov.:

AF XY:

0.329

AC XY:

24482

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.381

Hom.:

29306

Bravo

AF:

0.337

TwinsUK

AF:

0.374

AC:

1386

ALSPAC

AF:

0.375

AC:

1444

ESP6500AA

AF:

0.158

AC:

695

ESP6500EA

AF:

0.382

AC:

3287

ExAC

AF:

0.369

AC:

44788

Asia WGS

AF:

0.358

AC:

1243

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 27

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-7.9

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.26

MPC

0.36

ClinPred

0.038

GERP RS

4.5

Varity_R

0.62

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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