12-48904557-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033124.5(CCDC65):c.132+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,485,528 control chromosomes in the GnomAD database, including 212,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19439 hom., cov: 31)
  • Exomes 𝑓: 0.53 (192639 hom.)
• Consequence: CCDC65 NM_033124.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-48904557-C-T is Benign according to our data. Variant chr12-48904557-C-T is described in ClinVar as [Benign]. Clinvar id is 1277276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.132+89C>T		intron_variant		ENST00000320516.5
CCDC65	NM_001286957.2	c.-280+111C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.132+89C>T		intron_variant		1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.132+89C>T		intron_variant		5		A2
CCDC65	ENST00000552942.5	c.132+89C>T		intron_variant		5
CCDC65	ENST00000547861.5	c.110+111C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76221 AN: 151830 Hom.: 19434 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.534 AC: 712434 AN: 1333580 Hom.: 192639 AF XY: 0.539 AC XY: 353987 AN XY: 656254

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.502 AC: 76264 AN: 151948 Hom.: 19439 Cov.: 31 AF XY: 0.502 AC XY: 37283 AN XY: 74252

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.483

Alfa AF: 0.512 Hom.: 14119

Bravo AF: 0.484

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	11
Dann	Benign	0.78

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: rs3825184; hg19: chr12-49298340; COSMIC: COSV57196401; COSMIC: COSV57196401;