3-191358113-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_178335.3(CCDC50):c.228C>T(p.Arg76Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,326 control chromosomes in the GnomAD database, including 77,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6804 hom., cov: 31)

Exomes 𝑓: 0.31 ( 70808 hom. )

Consequence

CCDC50
NM_178335.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0720

Publications

20 publications found

Variant links:

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]

CCDC50 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 44
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CCDC50 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 3-191358113-C-T is Benign according to our data. Variant chr3-191358113-C-T is described in ClinVar as Benign. ClinVar VariationId is 48153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.072 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CCDC50	NM_178335.3 link	c.228C>T	p.Arg76Arg	synonymous_variant	Exon 3 of 12	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4 link	c.228C>T	p.Arg76Arg	synonymous_variant	Exon 3 of 11		NP_777568.1
CCDC50	XM_011512460.2 link	c.228C>T	p.Arg76Arg	synonymous_variant	Exon 3 of 8		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.228C>T	p.Arg76Arg	synonymous_variant	Exon 3 of 12	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4 link	c.228C>T	p.Arg76Arg	synonymous_variant	Exon 3 of 11	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45350

AN:

151782

Hom.:

6791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.302

AC:

75895

AN:

250986

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.309

AC:

451791

AN:

1461426

Hom.:

70808

Cov.:

AF XY:

0.307

AC XY:

223342

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.248

AC:

8285

AN:

33460

American (AMR)

AF:

0.323

AC:

14454

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

9525

AN:

26122

East Asian (EAS)

AF:

0.208

AC:

8258

AN:

39690

South Asian (SAS)

AF:

0.240

AC:

20721

AN:

86256

European-Finnish (FIN)

AF:

0.325

AC:

17355

AN:

53400

Middle Eastern (MID)

AF:

0.239

AC:

1379

AN:

5762

European-Non Finnish (NFE)

AF:

0.318

AC:

353519

AN:

1111668

Other (OTH)

AF:

0.303

AC:

18295

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16652

33304

49955

66607

83259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11436

22872

34308

45744

57180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

45414

AN:

151900

Hom.:

6804

Cov.:

AF XY:

0.300

AC XY:

22270

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.258

AC:

10688

AN:

41424

American (AMR)

AF:

0.307

AC:

4677

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1275

AN:

3468

East Asian (EAS)

AF:

0.249

AC:

1284

AN:

5156

South Asian (SAS)

AF:

0.226

AC:

1081

AN:

4780

European-Finnish (FIN)

AF:

0.332

AC:

3510

AN:

10572

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21948

AN:

67932

Other (OTH)

AF:

0.314

AC:

663

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1607

3214

4821

6428

8035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.315

Hom.:

6575

Bravo

AF:

0.300

Asia WGS

AF:

0.279

AC:

968

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg76Arg in Exon 03 of CCDC50: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 32.0% (2245/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11542549).

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.072

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over