3-191329946-G-T

Variant names:

• chr3-191329946-G-T
• rs796791217
• NM_178335.3:c.49+223G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_178335.3(CCDC50):​c.49+223G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00837 in 100,126 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0084 (14 hom., cov: 22)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 838 AD,Unknown gene.

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+223G>T		intron	N/A	NP_848018.1	Q8IVM0-2
	UTS2B	NM_198152.5	MANE Select	c.-665+468C>A		intron	N/A	NP_937795.2	Q765I0
	CCDC50	NM_174908.4		c.49+223G>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+223G>T		intron	N/A	ENSP00000376249.4	Q8IVM0-2
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-665+468C>A		intron	N/A	ENSP00000340526.5	Q765I0
	CCDC50	ENST00000392456.4	TSL:1	c.49+223G>T		intron	N/A	ENSP00000376250.4	Q8IVM0-1

Frequencies

GnomAD3 genomes AF: 0.00838 AC: 838 AN: 100052 Hom.: 14 Cov.: 22

Gnomad AFR AF: 0.00482

Gnomad AMI AF: 0.00239

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.00178

Gnomad EAS AF: 0.00183

Gnomad SAS AF: 0.00762

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.00521

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00567

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

GnomAD4 genome AF: 0.00837 AC: 838 AN: 100126 Hom.: 14 Cov.: 22 AF XY: 0.00761 AC XY: 370 AN XY: 48632

African (AFR) AF: 0.00480 AC: 80 AN: 16666

American (AMR) AF: 0.00778 AC: 76 AN: 9764

Ashkenazi Jewish (ASJ) AF: 0.00178 AC: 5 AN: 2804

East Asian (EAS) AF: 0.00184 AC: 3 AN: 1630

South Asian (SAS) AF: 0.00763 AC: 21 AN: 2754

European-Finnish (FIN) AF: 0.00158 AC: 14 AN: 8834

Middle Eastern (MID) AF: 0.00575 AC: 1 AN: 174

European-Non Finnish (NFE) AF: 0.0114 AC: 628 AN: 55234

Other (OTH) AF: 0.00560 AC: 8 AN: 1428

Alfa AF: 0.000766 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.57
PhyloP100		0.33
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: rs796791217; hg19: chr3-191047735;