chr3-191375496-G-T

Position:

chr3-191375496-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178335.3(CCDC50):c.883G>T(p.Asp295Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,652 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 62 hom. )

Consequence

CCDC50
NM_178335.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003019601).

BP6

Variant 3-191375496-G-T is Benign according to our data. Variant chr3-191375496-G-T is described in ClinVar as [Benign]. Clinvar id is 162857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191375496-G-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3 linkuse as main transcript	c.883G>T	p.Asp295Tyr	missense_variant	6/12	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	XM_011512460.2 linkuse as main transcript	c.883G>T	p.Asp295Tyr	missense_variant	6/8		XP_011510762.1
CCDC50	NM_174908.4 linkuse as main transcript	c.449-4663G>T		intron_variant			NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 linkuse as main transcript	c.883G>T	p.Asp295Tyr	missense_variant	6/12	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 linkuse as main transcript	c.449-4663G>T		intron_variant		1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

206

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0369

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00265

AC:

662

AN:

250228

Hom.:

AF XY:

0.00252

AC XY:

341

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0348

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.00162

AC:

2361

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1137

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0564

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152158

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0368

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00254

AC:

309

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 02, 2015

p.Asp295Tyr in exon 06 of CCDC50: This variant is not expected to have clinical significance because it has been identified in 3.5% (296/8576) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs75123867). -

Autosomal dominant nonsyndromic hearing loss 44

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

Polyphen

0.99

ClinPred

0.065

GERP RS

4.0

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over