chr3-191357007-TA-T

Variant names:

• chr3-191357007-TA-T
• rs879004278
• NM_178335.3:c.50-69delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_178335.3(CCDC50):​c.50-69delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 556,316 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.26 (1 hom.)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.50-69delA		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.50-69delA		intron_variant	Intron 1 of 10		NP_777568.1
CCDC50	XM_011512460.2	c.50-69delA		intron_variant	Intron 1 of 7		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.50-80delA		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4	c.50-80delA		intron_variant	Intron 1 of 10	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 364 AN: 145410 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00398

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.000789

Gnomad SAS AF: 0.00174

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00136

Gnomad OTH AF: 0.000508

GnomAD4 exome AF: 0.260 AC: 106764 AN: 410842 Hom.: 1 AF XY: 0.266 AC XY: 57152 AN XY: 215130

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.00252 AC: 366 AN: 145474 Hom.: 2 Cov.: 32 AF XY: 0.00291 AC XY: 206 AN XY: 70708

Gnomad4 AFR AF: 0.00416

Gnomad4 AMR AF: 0.00397

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.000791

Gnomad4 SAS AF: 0.00174

Gnomad4 FIN AF: 0.00391

Gnomad4 NFE AF: 0.00136

Gnomad4 OTH AF: 0.000503

Alfa AF: 0.000387 Hom.: 0

ClinVar

Not reported in ClinVar

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: rs879004278; hg19: chr3-191074796;