Variant 12-48914559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_033124.5(CCDC65):c.456G>A(p.Glu152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,614,018 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 0.00062 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

CCDC65
NM_033124.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.06

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 12-48914559-G-A is Benign according to our data. Variant chr12-48914559-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC65	NM_033124.5 linkuse as main transcript	c.456G>A	p.Glu152=	synonymous_variant	3/8	ENST00000320516.5	NP_149115.2
CCDC65	NM_001286957.2 linkuse as main transcript	c.27G>A	p.Glu9=	synonymous_variant	3/8		NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 linkuse as main transcript	c.456G>A	p.Glu152=	synonymous_variant	3/8	1	NM_033124.5	ENSP00000312706	P2	Q8IXS2-1
CCDC65	ENST00000266984.9 linkuse as main transcript	c.456G>A	p.Glu152=	synonymous_variant	3/9	5		ENSP00000266984	A2	Q8IXS2-2
CCDC65	ENST00000552942.5 linkuse as main transcript	c.301-3716G>A		intron_variant		5		ENSP00000446569
CCDC65	ENST00000547861.5 linkuse as main transcript	c.*287G>A		3_prime_UTR_variant, NMD_transcript_variant	3/8	2		ENSP00000447157

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000805

AC:

202

AN:

251052

Hom.:

AF XY:

0.000810

AC XY:

110

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00537

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000671

AC:

981

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

468

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000683

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000624

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000953

Hom.:

Bravo

AF:

0.000604

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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	Fulgent Genetics, Fulgent Genetics	May 16, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.3

DANN

Benign

0.76

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