rs10875894

Variant names:

• chr12-48921079-C-A
• rs10875894
• NM_033124.5:c.1176C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-48921079-C-A
• chr12-48921079-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033124.5(CCDC65):​c.1176C>A​(p.Thr392Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,902 control chromosomes in the GnomAD database, including 114,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9119 hom., cov: 31)
  • Exomes 𝑓: 0.37 (105828 hom.)
• Consequence: CCDC65 NM_033124.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0960

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-48921079-C-A is Benign according to our data. Variant chr12-48921079-C-A is described in ClinVar as [Benign]. Clinvar id is 402503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC65	NM_033124.5	c.1176C>A	p.Thr392Thr	synonymous_variant	Exon 7 of 8	ENST00000320516.5	NP_149115.2
CCDC65	NM_001286957.2	c.747C>A	p.Thr249Thr	synonymous_variant	Exon 7 of 8		NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5	c.1176C>A	p.Thr392Thr	synonymous_variant	Exon 7 of 8	1	NM_033124.5	ENSP00000312706.4
ENSG00000272822	ENST00000398092.4	c.385-17171G>T		intron_variant	Intron 4 of 4	3		ENSP00000438507.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49549 AN: 151890 Hom.: 9111 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.382 AC: 95332 AN: 249870 Hom.: 19790 AF XY: 0.373 AC XY: 50460 AN XY: 135228

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.437

Gnomad EAS exome AF: 0.466

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.375 AC: 546543 AN: 1457894 Hom.: 105828 Cov.: 44 AF XY: 0.371 AC XY: 269081 AN XY: 724668

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.326 AC: 49568 AN: 152008 Hom.: 9119 Cov.: 31 AF XY: 0.330 AC XY: 24508 AN XY: 74296

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.360

Alfa AF: 0.380 Hom.: 14474

Bravo AF: 0.337

Asia WGS AF: 0.358 AC: 1242 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.392

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 27 Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.78
DANN	Benign	0.68

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: rs10875894; hg19: chr12-49314862; COSMIC: COSV56739601; COSMIC: COSV56739601;