Genetic Variant NM_178335.3:c.49+233dupG (chr3-191329942-T-TG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_178335.3(CCDC50):c.49+233dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 0)

Consequence

CCDC50
NM_178335.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.702

Publications

0 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 links:

UTS2B (HGNC:30894): (urotensin 2B) Predicted to enable G protein-coupled receptor binding activity. Predicted to be involved in regulation of blood pressure. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

UTS2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.49+233dupG		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1	Q8IVM0-2
UTS2B	NM_198152.5 link	c.-665+471dupC		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2	Q765I0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC50	ENST00000392455.9 link	c.49+219_49+220insG	intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4	Q8IVM0-2
UTS2B	ENST00000340524.10 link	c.-665+471_-665+472insC	intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5	Q765I0
CCDC50	ENST00000392456.4 link	c.49+219_49+220insG	intron_variant	Intron 1 of 10	1		ENSP00000376250.4	Q8IVM0-1
UTS2B	ENST00000432514.5 link	c.-832+471_-832+472insC	intron_variant	Intron 1 of 6	5		ENSP00000401028.1	C9JU87

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

250

AN:

102758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.0304

Gnomad AMR

AF:

0.000995

Gnomad ASJ

AF:

0.00241

Gnomad EAS

AF:

0.00349

Gnomad SAS

AF:

0.00184

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.00223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00244

AC:

251

AN:

102830

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

119

AN XY:

48296

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000752

AC:

AN:

33262

American (AMR)

AF:

0.000993

AC:

AN:

10072

Ashkenazi Jewish (ASJ)

AF:

0.00241

AC:

AN:

2494

East Asian (EAS)

AF:

0.00350

AC:

AN:

4282

South Asian (SAS)

AF:

0.00185

AC:

AN:

3252

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

3530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.00383

AC:

168

AN:

43916

Other (OTH)

AF:

0.00222

AC:

AN:

1354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over