12-48904479-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033124.5(CCDC65):c.132+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,613,334 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (8 hom.)
• Consequence: CCDC65 NM_033124.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.386

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 12-48904479-T-C is Benign according to our data. Variant chr12-48904479-T-C is described in ClinVar as [Benign]. Clinvar id is 1600885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.132+11T>C		intron_variant		ENST00000320516.5
CCDC65	NM_001286957.2	c.-280+33T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.132+11T>C		intron_variant		1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.132+11T>C		intron_variant		5		A2
CCDC65	ENST00000552942.5	c.132+11T>C		intron_variant		5
CCDC65	ENST00000547861.5	c.110+33T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152054 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00177 AC: 438 AN: 248042 Hom.: 5 AF XY: 0.00205 AC XY: 275 AN XY: 134294

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00426

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00211

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00207 AC: 3022 AN: 1461162 Hom.: 8 Cov.: 32 AF XY: 0.00220 AC XY: 1598 AN XY: 726890

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00450

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00219

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00145 AC: 220 AN: 152172 Hom.: 1 Cov.: 31 AF XY: 0.00125 AC XY: 93 AN XY: 74398

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00312

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00192 Hom.: 0

Bravo AF: 0.00121

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 27 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	14
Dann	Benign	0.89

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

Other links and lift over

dbSNP: rs201804778; hg19: chr12-49298262;