3-191329942-TGG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178335.3(CCDC50):c.49+232_49+233del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (1396 hom., cov: 0)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.55

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-191329942-TGG-T is Benign according to our data. Variant chr3-191329942-TGG-T is described in ClinVar as [Benign]. Clinvar id is 1280397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC50	NM_178335.3	c.49+232_49+233del		intron_variant		ENST00000392455.9
UTS2B	NM_198152.5	c.-665+470_-665+471del		intron_variant		ENST00000340524.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTS2B	ENST00000340524.10	c.-665+470_-665+471del		intron_variant		2	NM_198152.5	P1
CCDC50	ENST00000392455.9	c.49+232_49+233del		intron_variant		1	NM_178335.3	P3
CCDC50	ENST00000392456.4	c.49+232_49+233del		intron_variant		1		A1
UTS2B	ENST00000432514.5	c.-832+470_-832+471del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 17531 AN: 102330 Hom.: 1394 Cov.: 0

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00209

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.171 AC: 17547 AN: 102398 Hom.: 1396 Cov.: 0 AF XY: 0.169 AC XY: 8105 AN XY: 48048

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.00210

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs34226642; hg19: chr3-191047731;