12-48904276-G-A

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.-61G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,562,848 control chromosomes in the GnomAD database, including 110,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9085 hom., cov: 30)
  • Exomes 𝑓: 0.37 (101655 hom.)
• Consequence: CCDC65 NM_033124.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.277

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=-0.79).
• BP6: Variant 12-48904276-G-A is Benign according to our data. Variant chr12-48904276-G-A is described in ClinVar as [Benign]. Clinvar id is 1294651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.-61G>A		5_prime_UTR_variant	1/8	ENST00000320516.5
CCDC65	NM_001286957.2	c.-450G>A		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.-61G>A		5_prime_UTR_variant	1/8	1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.-61G>A		5_prime_UTR_variant	1/9	5		A2
CCDC65	ENST00000552942.5	c.-61G>A		5_prime_UTR_variant	1/6	5
CCDC65	ENST00000547861.5	c.-61G>A		5_prime_UTR_variant, NMD_transcript_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49425 AN: 151768 Hom.: 9076 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.374 AC: 527141 AN: 1410960 Hom.: 101655 Cov.: 31 AF XY: 0.370 AC XY: 258939 AN XY: 699354

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.474

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.326 AC: 49447 AN: 151888 Hom.: 9085 Cov.: 30 AF XY: 0.329 AC XY: 24440 AN XY: 74252

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.361

Alfa AF: 0.375 Hom.: 15501

Bravo AF: 0.337

Asia WGS AF: 0.358 AC: 1242 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

May 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.4
Dann	Benign	0.84

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: rs3809147; hg19: chr12-49298059; COSMIC: COSV57194957; COSMIC: COSV57194957;