3-191329612-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178335.3(CCDC50):c.-63C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,553,974 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (46 hom.)
• Consequence: CCDC50 NM_178335.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-191329612-C-G is Benign according to our data. Variant chr3-191329612-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00374 (570/152290) while in subpopulation EAS AF= 0.0452 (234/5172). AF 95% confidence interval is 0.0405. There are 7 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 570 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC50	NM_178335.3	c.-63C>G		5_prime_UTR_variant	1/12	ENST00000392455.9
UTS2B	NM_198152.5	c.-665+802G>C		intron_variant		ENST00000340524.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC50	ENST00000392455.9	c.-63C>G		5_prime_UTR_variant	1/12	1	NM_178335.3	P3
UTS2B	ENST00000340524.10	c.-665+802G>C		intron_variant		2	NM_198152.5	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 570 AN: 152178 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00213 AC: 2991 AN: 1401684 Hom.: 46 Cov.: 27 AF XY: 0.00214 AC XY: 1483 AN XY: 694254

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.0000809

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0423

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152290 Hom.: 7 Cov.: 33 AF XY: 0.00495 AC XY: 369 AN XY: 74476

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00170 Hom.: 1

Bravo AF: 0.00209

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	9.5
Dann	Benign	0.82

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: rs377067940; hg19: chr3-191047401; COSMIC: COSV61280766; COSMIC: COSV61280766;