Genetic Variant NM_178335.3:c.50-70_50-69dupAA (chr3-191357007-T-TAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_178335.3(CCDC50):c.50-70_50-69dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000498 in 762,788 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

Variant links:

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]

CCDC50 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.50-70_50-69dupAA	intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.50-70_50-69dupAA	intron_variant	Intron 1 of 10		NP_777568.1	Q8IVM0-1
CCDC50	XM_011512460.2 link	c.50-70_50-69dupAA	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 link	c.50-81_50-80insAA		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.50-81_50-80insAA		intron_variant	Intron 1 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.0000685

AC:

AN:

146008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000788

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000454

AC:

AN:

616780

Hom.:

AF XY:

0.0000548

AC XY:

AN XY:

328712

show subpopulations

Gnomad4 AFR exome

AF:

0.000202

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000570

Gnomad4 EAS exome

AF:

0.0000736

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000253

Gnomad4 NFE exome

AF:

0.0000479

Gnomad4 OTH exome

AF:

0.0000330

GnomAD4 genome

AF:

0.0000685

AC:

AN:

146008

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

70942

show subpopulations

Gnomad4 AFR

AF:

0.000150

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000788

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over