12-48904278-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033124.5(CCDC65):c.-59T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,570,232 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (38 hom., cov: 31)
  • Exomes 𝑓: 0.00088 (23 hom.)
• Consequence: CCDC65 NM_033124.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.561

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=-0.81).
• BP6: Variant 12-48904278-T-C is Benign according to our data. Variant chr12-48904278-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1198595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1531/152128) while in subpopulation AFR AF= 0.0356 (1478/41516). AF 95% confidence interval is 0.0341. There are 38 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.-59T>C		5_prime_UTR_variant	1/8	ENST00000320516.5
CCDC65	NM_001286957.2	c.-448T>C		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.-59T>C		5_prime_UTR_variant	1/8	1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.-59T>C		5_prime_UTR_variant	1/9	5		A2
CCDC65	ENST00000552942.5	c.-59T>C		5_prime_UTR_variant	1/6	5
CCDC65	ENST00000547861.5	c.-59T>C		5_prime_UTR_variant, NMD_transcript_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1531 AN: 152010 Hom.: 38 Cov.: 31

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.000880 AC: 1248 AN: 1418104 Hom.: 23 Cov.: 32 AF XY: 0.000755 AC XY: 531 AN XY: 703516

Gnomad4 AFR exome AF: 0.0358

Gnomad4 AMR exome AF: 0.000980

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000618

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000128

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.0101 AC: 1531 AN: 152128 Hom.: 38 Cov.: 31 AF XY: 0.00990 AC XY: 736 AN XY: 74374

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00223

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00863 Hom.: 3

Bravo AF: 0.0113

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.4
Dann	Benign	0.66

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: rs74088529; hg19: chr12-49298061;