3-191329942-TGGGGGG-TGGGGG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Genomes: 𝑓 0.084 (173 hom., cov: 0)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-191329942-TG-T is Benign according to our data. Variant chr3-191329942-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1266348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+233delG		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+471delC		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+220delG		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-665+471delC		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392456.4	c.49+220delG		intron_variant	Intron 1 of 10	1		ENSP00000376250.4
UTS2B	ENST00000432514.5	c.-832+471delC		intron_variant	Intron 1 of 6	5		ENSP00000401028.1

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 8511 AN: 101622 Hom.: 172 Cov.: 0

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0946

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0837 AC: 8511 AN: 101678 Hom.: 173 Cov.: 0 AF XY: 0.0812 AC XY: 3877 AN XY: 47722

African (AFR) AF: 0.0844 AC: 2747 AN: 32544

American (AMR) AF: 0.0665 AC: 663 AN: 9976

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 305 AN: 2466

East Asian (EAS) AF: 0.0169 AC: 72 AN: 4270

South Asian (SAS) AF: 0.0764 AC: 246 AN: 3222

European-Finnish (FIN) AF: 0.0791 AC: 277 AN: 3504

Middle Eastern (MID) AF: 0.0971 AC: 20 AN: 206

European-Non Finnish (NFE) AF: 0.0910 AC: 3977 AN: 43688

Other (OTH) AF: 0.0964 AC: 130 AN: 1348

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;