Genetic Variant CCDC50:c.-63C>T (chr3-191329612-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178335.3(CCDC50):c.-63C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CCDC50
NM_178335.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC50	NM_178335.3	MANE Select	c.-63C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_848018.1	Q8IVM0-2
CCDC50	NM_178335.3	MANE Select	c.-63C>T	5_prime_UTR	Exon 1 of 12	NP_848018.1	Q8IVM0-2
UTS2B	NM_198152.5	MANE Select	c.-665+802G>A	intron	N/A	NP_937795.2	Q765I0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.-63C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000376249.4	Q8IVM0-2
CCDC50	ENST00000392456.4	TSL:1	c.-63C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000376250.4	Q8IVM0-1
CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.-63C>T	5_prime_UTR	Exon 1 of 12	ENSP00000376249.4	Q8IVM0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1401698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694266

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31144

American (AMR)

AF:

0.00

AC:

AN:

37072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24974

East Asian (EAS)

AF:

0.00

AC:

AN:

37000

South Asian (SAS)

AF:

0.00

AC:

AN:

80098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078476

Other (OTH)

AF:

0.00

AC:

AN:

58162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.16

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over