rs118060953

Positions:

chr12-48905016-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033124.5(CCDC65):c.203T>C(p.Val68Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00143 in 1,614,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

CCDC65
NM_033124.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.38

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01739201).

BP6

Variant 12-48905016-T-C is Benign according to our data. Variant chr12-48905016-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5 linkuse as main transcript	c.203T>C	p.Val68Ala	missense_variant	2/8	ENST00000320516.5
CCDC65	NM_001286957.2 linkuse as main transcript	c.-227T>C		5_prime_UTR_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5 linkuse as main transcript	c.203T>C	p.Val68Ala	missense_variant	2/8	1	NM_033124.5	P2	Q8IXS2-1
CCDC65	ENST00000266984.9 linkuse as main transcript	c.203T>C	p.Val68Ala	missense_variant	2/9	5		A2	Q8IXS2-2
CCDC65	ENST00000552942.5 linkuse as main transcript	c.203T>C	p.Val68Ala	missense_variant	2/6	5
CCDC65	ENST00000547861.5 linkuse as main transcript	c.*34T>C		3_prime_UTR_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

251394

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00145

AC:

2125

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

996

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.00171

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00121

AC:

185

AN:

152274

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00256

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00118

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00141

AC:

171

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 27

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 09, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CCDC65: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.72

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.055

T;D;T

Polyphen

0.87

.;.;P

Vest4

0.24

MVP

0.10

MPC

0.069

ClinPred

0.033

GERP RS

5.0

Varity_R

0.44

gMVP

0.22

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