rs10783293

Positions:

• chr12-48914692-G-A
• chr12-48914692-G-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.470+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 867,758 control chromosomes in the GnomAD database, including 76,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12624 hom., cov: 31)
  • Exomes 𝑓: 0.41 (63464 hom.)
• Consequence: CCDC65 NM_033124.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.297

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]

ENSG00000272822 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-48914692-G-A is Benign according to our data. Variant chr12-48914692-G-A is described in ClinVar as [Benign]. Clinvar id is 1250781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC65	NM_033124.5	c.470+119G>A		intron_variant		ENST00000320516.5	NP_149115.2
CCDC65	NM_001286957.2	c.41+119G>A		intron_variant			NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5	c.470+119G>A		intron_variant		1	NM_033124.5	ENSP00000312706.4
ENSG00000272822	ENST00000398092.4	c.385-10784C>T		intron_variant		3		ENSP00000438507.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59933 AN: 151780 Hom.: 12616 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.413 AC: 295633 AN: 715862 Hom.: 63464 AF XY: 0.407 AC XY: 147545 AN XY: 362412

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.395 AC: 59961 AN: 151896 Hom.: 12624 Cov.: 31 AF XY: 0.398 AC XY: 29563 AN XY: 74220

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.419

Alfa AF: 0.442 Hom.: 15106

Bravo AF: 0.400

Asia WGS AF: 0.370 AC: 1286 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	-0.96
CADD	Benign	0.58
DANN	Benign	0.70

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: rs10783293; hg19: chr12-49308475; COSMIC: COSV57194486; COSMIC: COSV57194486;