12-48904720-T-C

Position:

• chr12-48904720-T-C

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.133-226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,104 control chromosomes in the GnomAD database, including 9,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9148 hom., cov: 32)
• Consequence: CCDC65 NM_033124.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.284

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 12-48904720-T-C is Benign according to our data. Variant chr12-48904720-T-C is described in ClinVar as [Benign]. Clinvar id is 1236502.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	Protein	UniProt
CCDC65	NM_033124.5	c.133-226T>C		intron_variant		ENST00000320516.5	NP_149115.2
CCDC65	NM_001286957.2	c.-279-244T>C		intron_variant			NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5	c.133-226T>C		intron_variant		1	NM_033124.5	ENSP00000312706.4
ENSG00000272822	ENST00000398092.4	c.385-812A>G		intron_variant		3		ENSP00000438507.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49713 AN: 151986 Hom.: 9140 Cov.: 32

Gnomad AFR AF: 0.161

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49732 AN: 152104 Hom.: 9148 Cov.: 32 AF XY: 0.330 AC XY: 24571 AN XY: 74350

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.474

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: 0.342 Hom.: 1177

Bravo AF: 0.338

Asia WGS AF: 0.359 AC: 1246 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	6.2
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4760665; hg19: chr12-49298503;