3-191329453-C-T

Variant names:

• chr3-191329453-C-T
• rs56141214
• NM_178335.3:c.-222C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.-222C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-664-744G>A		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.-222C>T		5_prime_UTR_variant	Exon 1 of 12	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-664-744G>A		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5

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

African (AFR) AF: 0.00183 AC: 12 AN: 6572

American (AMR) AF: 0.00353 AC: 24 AN: 6800

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 117 AN: 9460

East Asian (EAS) AF: 0.00 AC: 0 AN: 20828

South Asian (SAS) AF: 0.00416 AC: 83 AN: 19934

European-Finnish (FIN) AF: 0.0146 AC: 462 AN: 31694

Middle Eastern (MID) AF: 0.00336 AC: 5 AN: 1486

European-Non Finnish (NFE) AF: 0.0132 AC: 2604 AN: 197476

Other (OTH) AF: 0.0115 AC: 217 AN: 18854

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

African (AFR) AF: 0.00250 AC: 104 AN: 41584

American (AMR) AF: 0.00549 AC: 84 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4830

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 882 AN: 67998

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 23, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.089
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism

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: rs56141214; hg19: chr3-191047242;