3-191329292-G-A

Position:

• chr3-191329292-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000392456.4(CCDC50):​c.-383G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 203,228 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (0 hom.)
• Consequence: CCDC50 ENST00000392456.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-191329292-G-A is Benign according to our data. Variant chr3-191329292-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 540 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTS2B	NM_198152.5	c.-664-583C>T		intron_variant		ENST00000340524.10	NP_937795.2
UTS2B	XM_047447899.1	c.-260-583C>T		intron_variant			XP_047303855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10	c.-664-583C>T		intron_variant		2	NM_198152.5	ENSP00000340526	P1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152236 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00536

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00421 AC: 214 AN: 50874 Hom.: 0 Cov.: 0 AF XY: 0.00429 AC XY: 110 AN XY: 25642

Gnomad4 AFR exome AF: 0.000700

Gnomad4 AMR exome AF: 0.00647

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00415

Gnomad4 NFE exome AF: 0.00524

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.00354 AC: 540 AN: 152354 Hom.: 2 Cov.: 33 AF XY: 0.00361 AC XY: 269 AN XY: 74496

Gnomad4 AFR AF: 0.000793

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00536

Gnomad4 NFE AF: 0.00548

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00805 Hom.: 2

Bravo AF: 0.00327

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

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs186382346; hg19: chr3-191047081;