3-191329954-G-T

Variant names:

• chr3-191329954-G-T
• rs115986233
• NM_178335.3:c.49+231G>T

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+231G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 138,290 control chromosomes in the GnomAD database, including 3,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (3215 hom., cov: 22)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.211
• Publications: 3 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=-0.82).
• BP6: Variant 3-191329954-G-T is Benign according to our data. Variant chr3-191329954-G-T is described in ClinVar as Benign. ClinVar VariationId is 1237149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.49+231G>T		intron	N/A	NP_848018.1	Q8IVM0-2
	UTS2B	NM_198152.5	MANE Select	c.-665+460C>A		intron	N/A	NP_937795.2	Q765I0
	CCDC50	NM_174908.4		c.49+231G>T		intron	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.49+231G>T		intron	N/A	ENSP00000376249.4	Q8IVM0-2
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-665+460C>A		intron	N/A	ENSP00000340526.5	Q765I0
	CCDC50	ENST00000392456.4	TSL:1	c.49+231G>T		intron	N/A	ENSP00000376250.4	Q8IVM0-1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 22961 AN: 138184 Hom.: 3210 Cov.: 22

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0292

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0883

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.166 AC: 22980 AN: 138290 Hom.: 3215 Cov.: 22 AF XY: 0.164 AC XY: 10939 AN XY: 66620

African (AFR) AF: 0.347 AC: 12940 AN: 37258

American (AMR) AF: 0.163 AC: 2197 AN: 13516

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 295 AN: 3340

East Asian (EAS) AF: 0.267 AC: 1163 AN: 4358

South Asian (SAS) AF: 0.155 AC: 616 AN: 3976

European-Finnish (FIN) AF: 0.0362 AC: 312 AN: 8608

Middle Eastern (MID) AF: 0.194 AC: 52 AN: 268

European-Non Finnish (NFE) AF: 0.0795 AC: 5103 AN: 64192

Other (OTH) AF: 0.144 AC: 277 AN: 1918

Alfa AF: 0.0181 Hom.: 61

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.68
PhyloP100		-0.21
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: rs115986233; hg19: chr3-191047743;