chr12-48918757-C-T

Variant names:

Variant summary

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

The NM_033124.5(CCDC65):c.880C>T(p.Arg294Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 1,613,972 control chromosomes in the GnomAD database, including 2,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 209 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2400 hom. )

Consequence

CCDC65
NM_033124.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.83

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=0.0017585754).

BP6

Variant 12-48918757-C-T is Benign according to our data. Variant chr12-48918757-C-T is described in ClinVar as [Benign]. Clinvar id is 262221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-48918757-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC65	NM_033124.5 link	c.880C>T	p.Arg294Cys	missense_variant	Exon 6 of 8	ENST00000320516.5	NP_149115.2	Q8IXS2-1
CCDC65	NM_001286957.2 link	c.451C>T	p.Arg151Cys	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.880C>T	p.Arg294Cys	missense_variant	Exon 6 of 8	1	NM_033124.5	ENSP00000312706.4		Q8IXS2-1
ENSG00000272822	ENST00000398092.4 link	c.385-14849G>A		intron_variant	Intron 4 of 4	3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6513

AN:

152024

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0613

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0415

AC:

10442

AN:

251482

Hom.:

338

AF XY:

0.0419

AC XY:

5700

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.0995

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0522

AC:

76358

AN:

1461830

Hom.:

2400

Cov.:

AF XY:

0.0511

AC XY:

37157

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00738

Gnomad4 AMR exome

AF:

0.0196

Gnomad4 ASJ exome

AF:

0.0197

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0981

Gnomad4 NFE exome

AF:

0.0591

Gnomad4 OTH exome

AF:

0.0448

GnomAD4 genome

AF:

0.0428

AC:

6511

AN:

152142

Hom.:

209

Cov.:

AF XY:

0.0446

AC XY:

3320

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.0332

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0613

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0508

Hom.:

409

Bravo

AF:

0.0346

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0607

AC:

234

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.0555

AC:

477

ExAC

AF:

0.0413

AC:

5008

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0534

EpiControl

AF:

0.0520

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 24, 2019

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 27

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

.;.;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.26

MPC

0.37

ClinPred

0.026

GERP RS

4.7

Varity_R

0.21

gMVP

0.31

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