chr3-191357007-T-TA

Position:

• chr3-191357007-T-TA

Variant summary

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

The NM_178335.3(CCDC50):​c.50-69dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 753,264 control chromosomes in the GnomAD database, including 121 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (119 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (2 hom.)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-191357007-T-TA is Benign according to our data. Variant chr3-191357007-T-TA is described in ClinVar as [Benign]. Clinvar id is 1271942.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.50-69dup		intron_variant		ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.50-69dup		intron_variant			NP_777568.1
CCDC50	XM_011512460.2	c.50-69dup		intron_variant			XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.50-69dup		intron_variant		1	NM_178335.3	ENSP00000376249	P3
CCDC50	ENST00000392456.4	c.50-69dup		intron_variant		1		ENSP00000376250	A1

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3364 AN: 145980 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.000217

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000394

Gnomad OTH AF: 0.0121

GnomAD4 exome AF: 0.00830 AC: 5039 AN: 607210 Hom.: 2 AF XY: 0.00745 AC XY: 2411 AN XY: 323662

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.00320

Gnomad4 EAS exome AF: 0.00288

Gnomad4 SAS exome AF: 0.00287

Gnomad4 FIN exome AF: 0.00446

Gnomad4 NFE exome AF: 0.00711

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0231 AC: 3369 AN: 146054 Hom.: 119 Cov.: 32 AF XY: 0.0234 AC XY: 1665 AN XY: 71022

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000218

Gnomad4 FIN AF: 0.000109

Gnomad4 NFE AF: 0.000395

Gnomad4 OTH AF: 0.0120

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 18, 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: rs879004278; hg19: chr3-191074796;