Variant 12-48918810-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033124.5(CCDC65):c.933A>G(p.Arg311=) 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 1,613,438 control chromosomes in the GnomAD database, including 115,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9126 hom., cov: 31)

Exomes 𝑓: 0.38 ( 106264 hom. )

Consequence

CCDC65
NM_033124.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.12

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=-0.66).

BP6

Variant 12-48918810-A-G is Benign according to our data. Variant chr12-48918810-A-G is described in ClinVar as [Benign]. Clinvar id is 402502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 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.933A>G	p.Arg311=	synonymous_variant	6/8	ENST00000320516.5
CCDC65	NM_001286957.2 linkuse as main transcript	c.504A>G	p.Arg168=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5 linkuse as main transcript	c.933A>G	p.Arg311=	synonymous_variant	6/8	1	NM_033124.5	P2	Q8IXS2-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49575

AN:

151930

Hom.:

9118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.382

AC:

96027

AN:

251420

Hom.:

19980

AF XY:

0.374

AC XY:

50773

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.375

AC:

548159

AN:

1461390

Hom.:

106264

Cov.:

AF XY:

0.372

AC XY:

270132

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.539

Gnomad4 ASJ exome

AF:

0.435

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:

49594

AN:

152048

Hom.:

9126

Cov.:

AF XY:

0.330

AC XY:

24502

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.365

Hom.:

6849

Bravo

AF:

0.337

Asia WGS

AF:

0.358

AC:

1243

AN:

3478

EpiCase

AF:

0.390

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

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.4

DANN

Benign

0.65

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