rs364519

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178335.3(CCDC50):c.1269C>A(p.Ser423Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,608,742 control chromosomes in the GnomAD database, including 199,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27042 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172218 hom. )

Consequence

CCDC50
NM_178335.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.494

Publications

31 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 3-191382772-C-A is Benign according to our data. Variant chr3-191382772-C-A is described in ClinVar as Benign. ClinVar VariationId is 48151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.494 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.1269C>A	p.Ser423Ser	synonymous_variant	Exon 10 of 12	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.741C>A	p.Ser247Ser	synonymous_variant	Exon 9 of 11		NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.1269C>A	p.Ser423Ser	synonymous_variant	Exon 10 of 12	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.741C>A	p.Ser247Ser	synonymous_variant	Exon 9 of 11	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87679

AN:

151810

Hom.:

26988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.547

GnomAD2 exomes

AF:

0.533

AC:

133673

AN:

250946

AF XY:

0.520

show subpopulations

Gnomad AFR exome

AF:

0.808

Gnomad AMR exome

AF:

0.626

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.507

GnomAD4 exome

AF:

0.480

AC:

699552

AN:

1456814

Hom.:

172218

Cov.:

AF XY:

0.479

AC XY:

347509

AN XY:

724928

show subpopulations

African (AFR)

AF:

0.813

AC:

27151

AN:

33376

American (AMR)

AF:

0.619

AC:

27654

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

13148

AN:

26074

East Asian (EAS)

AF:

0.645

AC:

25546

AN:

39632

South Asian (SAS)

AF:

0.517

AC:

44563

AN:

86140

European-Finnish (FIN)

AF:

0.444

AC:

23707

AN:

53382

Middle Eastern (MID)

AF:

0.467

AC:

2689

AN:

5756

European-Non Finnish (NFE)

AF:

0.456

AC:

505071

AN:

1107580

Other (OTH)

AF:

0.499

AC:

30023

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

17033

34066

51100

68133

85166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15320

30640

45960

61280

76600

<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:

0.578

AC:

87788

AN:

151928

Hom.:

27042

Cov.:

AF XY:

0.578

AC XY:

42893

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.806

AC:

33446

AN:

41490

American (AMR)

AF:

0.566

AC:

8615

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1750

AN:

3472

East Asian (EAS)

AF:

0.665

AC:

3439

AN:

5172

South Asian (SAS)

AF:

0.523

AC:

2517

AN:

4816

European-Finnish (FIN)

AF:

0.445

AC:

4677

AN:

10504

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.467

AC:

31716

AN:

67944

Other (OTH)

AF:

0.545

AC:

1150

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.520

Hom.:

22038

Bravo

AF:

0.599

Asia WGS

AF:

0.624

AC:

2168

AN:

3478

EpiCase

AF:

0.464

EpiControl

AF:

0.465

ClinVar

Significance: Benign

Submissions summary: Benign:6

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 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser423Ser in Exon 10 of CCDC50: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 46.1% (3233/7020) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs364519). -

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. -

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

- -

Autosomal dominant nonsyndromic hearing loss 44

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.7

(source)

DANN

Benign

0.57

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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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