3-191356994-AT-A

Position:

• chr3-191356994-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178335.3(CCDC50):​c.50-86del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 791,716 control chromosomes in the GnomAD database, including 3,271 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (531 hom., cov: 31)
  • Exomes 𝑓: 0.082 (2740 hom.)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

Genes affected

CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-191356994-AT-A is Benign according to our data. Variant chr3-191356994-AT-A is described in ClinVar as [Benign]. Clinvar id is 1235084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.50-86del		intron_variant		ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.50-86del		intron_variant			NP_777568.1
CCDC50	XM_011512460.2	c.50-86del		intron_variant			XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.50-86del		intron_variant		1	NM_178335.3	ENSP00000376249	P3
CCDC50	ENST00000392456.4	c.50-86del		intron_variant		1		ENSP00000376250	A1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11820 AN: 151324 Hom.: 528 Cov.: 31

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0824 AC: 52745 AN: 640276 Hom.: 2740 AF XY: 0.0824 AC XY: 28329 AN XY: 343652

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.0832

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0739

Gnomad4 OTH exome AF: 0.0928

GnomAD4 genome AF: 0.0782 AC: 11842 AN: 151440 Hom.: 531 Cov.: 31 AF XY: 0.0801 AC XY: 5926 AN XY: 73994

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.0332 Hom.: 18

Bravo AF: 0.0793

Asia WGS AF: 0.199 AC: 690 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

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs35377745; hg19: chr3-191074783;