NM_178335.3:c.49+232_49+233delGG

Variant names:

• chr3-191329942-TGG-T
• rs34226642
• NM_178335.3:c.49+232_49+233delGG

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+232_49+233delGG 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
• 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-TGG-T is Benign according to our data. Variant chr3-191329942-TGG-T is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+232_49+233delGG		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+470_-665+471delCC		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+220_49+221delGG		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-665+470_-665+471delCC		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392456.4	c.49+220_49+221delGG		intron_variant	Intron 1 of 10	1		ENSP00000376250.4
UTS2B	ENST00000432514.5	c.-832+470_-832+471delCC		intron_variant	Intron 1 of 6	5		ENSP00000401028.1

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

African (AFR) AF: 0.185 AC: 6131 AN: 33152

American (AMR) AF: 0.167 AC: 1658 AN: 9954

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 480 AN: 2486

East Asian (EAS) AF: 0.00210 AC: 9 AN: 4284

South Asian (SAS) AF: 0.0880 AC: 285 AN: 3240

European-Finnish (FIN) AF: 0.174 AC: 608 AN: 3496

Middle Eastern (MID) AF: 0.102 AC: 21 AN: 206

European-Non Finnish (NFE) AF: 0.184 AC: 8048 AN: 43764

Other (OTH) AF: 0.158 AC: 213 AN: 1352

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 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV61282127; COSMIC: COSV61282127;