3-191356994-ATT-ATTT

Variant names:

• chr3-191356994-A-AT
• rs35377745
• NM_178335.3:c.50-86dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_178335.3(CCDC50):​c.50-86dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 791,992 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00042 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.50-86dupT		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.50-86dupT		intron_variant	Intron 1 of 10		NP_777568.1
CCDC50	XM_011512460.2	c.50-86dupT		intron_variant	Intron 1 of 7		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.50-94_50-93insT		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4	c.50-94_50-93insT		intron_variant	Intron 1 of 10	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes AF: 0.000423 AC: 64 AN: 151358 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 110 AN: 640518 Hom.: 0 AF XY: 0.000151 AC XY: 52 AN XY: 343764

Gnomad4 AFR exome AF: 0.000623

Gnomad4 AMR exome AF: 0.000115

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000235

Gnomad4 OTH exome AF: 0.0000904

GnomAD4 genome AF: 0.000423 AC: 64 AN: 151474 Hom.: 1 Cov.: 31 AF XY: 0.000365 AC XY: 27 AN XY: 74012

Gnomad4 AFR AF: 0.000997

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35377745; hg19: chr3-191074783;