NM_178335.3:c.49+219T>G

Variant names:

• chr3-191329942-T-G
• rs117340948
• NM_178335.3:c.49+219T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178335.3(CCDC50):​c.49+219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (4300 hom., cov: 14)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.794
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-191329942-T-G is Benign according to our data. Variant chr3-191329942-T-G is described in ClinVar as [Benign]. Clinvar id is 1236710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+219T>G		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+472A>C		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+219T>G		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-665+472A>C		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392456.4	c.49+219T>G		intron_variant	Intron 1 of 10	1		ENSP00000376250.4
UTS2B	ENST00000432514.5	c.-832+472A>C		intron_variant	Intron 1 of 6	5		ENSP00000401028.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 29925 AN: 102630 Hom.: 4294 Cov.: 14

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.371

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.292 AC: 29944 AN: 102694 Hom.: 4300 Cov.: 14 AF XY: 0.302 AC XY: 14560 AN XY: 48222

African (AFR) AF: 0.217 AC: 7193 AN: 33156

American (AMR) AF: 0.345 AC: 3471 AN: 10048

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 683 AN: 2498

East Asian (EAS) AF: 0.669 AC: 2851 AN: 4260

South Asian (SAS) AF: 0.471 AC: 1527 AN: 3244

European-Finnish (FIN) AF: 0.351 AC: 1238 AN: 3532

Middle Eastern (MID) AF: 0.365 AC: 76 AN: 208

European-Non Finnish (NFE) AF: 0.282 AC: 12402 AN: 43926

Other (OTH) AF: 0.298 AC: 405 AN: 1358

Alfa AF: 0.227 Hom.: 1011

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 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
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.60
PhyloP100		-0.79
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: rs117340948; hg19: chr3-191047731;