3-191329453-C-T

Position:

• chr3-191329453-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_178335.3(CCDC50):​c.-222C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 465,390 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (11 hom., cov: 33)
  • Exomes 𝑓: 0.011 (38 hom.)
• Consequence: CCDC50 NM_178335.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-191329453-C-T is Benign according to our data. Variant chr3-191329453-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1312 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC50	NM_178335.3	c.-222C>T		5_prime_UTR_variant	1/12	ENST00000392455.9
UTS2B	NM_198152.5	c.-664-744G>A		intron_variant		ENST00000340524.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC50	ENST00000392455.9	c.-222C>T		5_prime_UTR_variant	1/12	1	NM_178335.3	P3
UTS2B	ENST00000340524.10	c.-664-744G>A		intron_variant		2	NM_198152.5	P1

Frequencies

GnomAD3 genomes AF: 0.00861 AC: 1311 AN: 152178 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.0113 AC: 3524 AN: 313104 Hom.: 38 Cov.: 3 AF XY: 0.0108 AC XY: 1779 AN XY: 165130

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00416

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.00862 AC: 1312 AN: 152286 Hom.: 11 Cov.: 33 AF XY: 0.00839 AC XY: 625 AN XY: 74458

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00977 Hom.: 0

Bravo AF: 0.00751

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs56141214; hg19: chr3-191047242;