NM_178335.3:c.49+233dupG

Variant names:

• chr3-191329942-T-TG
• rs34226642
• NM_178335.3:c.49+233dupG

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 0 publications found

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]

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]

ACMG classification

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	c.49+233dupG		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+471dupC		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 250 AN: 102758 Hom.: 0 Cov.: 0

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.: 0 Cov.: 0 AF XY: 0.00246 AC XY: 119 AN XY: 48296

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

African (AFR) AF: 0.000752 AC: 25 AN: 33262

American (AMR) AF: 0.000993 AC: 10 AN: 10072

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 6 AN: 2494

East Asian (EAS) AF: 0.00350 AC: 15 AN: 4282

South Asian (SAS) AF: 0.00185 AC: 6 AN: 3252

European-Finnish (FIN) AF: 0.00113 AC: 4 AN: 3530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.00383 AC: 168 AN: 43916

Other (OTH) AF: 0.00222 AC: 3 AN: 1354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34226642; hg19: chr3-191047731;