rs10513865

Variant names:

• chr3-191371096-G-A
• rs10513865
• NM_178335.3:c.448+1060G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178335.3(CCDC50):​c.448+1060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,172 control chromosomes in the GnomAD database, including 415 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 0.052 (415 hom., cov: 31)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.448+1060G>A		intron_variant	Intron 5 of 11	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.448+1060G>A		intron_variant	Intron 5 of 10		NP_777568.1
CCDC50	XM_011512460.2	c.448+1060G>A		intron_variant	Intron 5 of 7		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.448+1060G>A		intron_variant	Intron 5 of 11	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4	c.448+1060G>A		intron_variant	Intron 5 of 10	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7847 AN: 152054 Hom.: 413 Cov.: 31

Gnomad AFR AF: 0.00835

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0516 AC: 7859 AN: 152172 Hom.: 415 Cov.: 31 AF XY: 0.0592 AC XY: 4400 AN XY: 74370

Gnomad4 AFR AF: 0.00833

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0402 Hom.: 224

Bravo AF: 0.0470

Asia WGS AF: 0.164 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.82

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: rs10513865; hg19: chr3-191088885;