rs145100370

chr12-48914559-G-Achr12-48914559-G-Cchr12-48914559-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_033124.5(CCDC65):c.456G>A(p.Glu152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,614,018 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (1 hom.)
• Consequence: CCDC65 NM_033124.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 12-48914559-G-A is Benign according to our data. Variant chr12-48914559-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.456G>A	p.Glu152=	synonymous_variant	3/8	ENST00000320516.5
CCDC65	NM_001286957.2	c.27G>A	p.Glu9=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.456G>A	p.Glu152=	synonymous_variant	3/8	1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.456G>A	p.Glu152=	synonymous_variant	3/9	5		A2
CCDC65	ENST00000552942.5	c.301-3716G>A		intron_variant		5
CCDC65	ENST00000547861.5	c.*287G>A		3_prime_UTR_variant, NMD_transcript_variant	3/8	2

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000805 AC: 202 AN: 251052 Hom.: 1 AF XY: 0.000810 AC XY: 110 AN XY: 135726

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000671 AC: 981 AN: 1461694 Hom.: 1 Cov.: 32 AF XY: 0.000644 AC XY: 468 AN XY: 727170

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00471

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000683

Gnomad4 OTH exome AF: 0.000861

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74482

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000953 Hom.: 0

Bravo AF: 0.000604

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 27 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 16, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	9.3
Dann	Benign	0.76

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: rs145100370; hg19: chr12-49308342;