rs364519

Variant names:

• chr3-191382772-C-A
• rs364519
• NM_178335.3:c.1269C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-191382772-C-A
• chr3-191382772-C-G
• chr3-191382772-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178335.3(CCDC50):​c.1269C>A​(p.Ser423Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,608,742 control chromosomes in the GnomAD database, including 199,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27042 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172218 hom.)
• Consequence: CCDC50 NM_178335.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.494
• Publications: 31 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]

CCDC50 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nonsyndromic hearing loss 44

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 3-191382772-C-A is Benign according to our data. Variant chr3-191382772-C-A is described in ClinVar as Benign. ClinVar VariationId is 48151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.494 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

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.1269C>A	p.Ser423Ser	synonymous	Exon 10 of 12	NP_848018.1	Q8IVM0-2
	CCDC50	NM_174908.4		c.741C>A	p.Ser247Ser	synonymous	Exon 9 of 11	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.1269C>A	p.Ser423Ser	synonymous	Exon 10 of 12	ENSP00000376249.4	Q8IVM0-2
	CCDC50	ENST00000392456.4	TSL:1	c.741C>A	p.Ser247Ser	synonymous	Exon 9 of 11	ENSP00000376250.4	Q8IVM0-1
	CCDC50	ENST00000899243.1		c.1356C>A	p.Ser452Ser	synonymous	Exon 11 of 13	ENSP00000569302.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87679 AN: 151810 Hom.: 26988 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.547

GnomAD2 exomes AF: 0.533 AC: 133673 AN: 250946 AF XY: 0.520

Gnomad AFR exome AF: 0.808

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.681

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.480 AC: 699552 AN: 1456814 Hom.: 172218 Cov.: 34 AF XY: 0.479 AC XY: 347509 AN XY: 724928

African (AFR) AF: 0.813 AC: 27151 AN: 33376

American (AMR) AF: 0.619 AC: 27654 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 13148 AN: 26074

East Asian (EAS) AF: 0.645 AC: 25546 AN: 39632

South Asian (SAS) AF: 0.517 AC: 44563 AN: 86140

European-Finnish (FIN) AF: 0.444 AC: 23707 AN: 53382

Middle Eastern (MID) AF: 0.467 AC: 2689 AN: 5756

European-Non Finnish (NFE) AF: 0.456 AC: 505071 AN: 1107580

Other (OTH) AF: 0.499 AC: 30023 AN: 60178

GnomAD4 genome AF: 0.578 AC: 87788 AN: 151928 Hom.: 27042 Cov.: 32 AF XY: 0.578 AC XY: 42893 AN XY: 74222

African (AFR) AF: 0.806 AC: 33446 AN: 41490

American (AMR) AF: 0.566 AC: 8615 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3439 AN: 5172

South Asian (SAS) AF: 0.523 AC: 2517 AN: 4816

European-Finnish (FIN) AF: 0.445 AC: 4677 AN: 10504

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.467 AC: 31716 AN: 67944

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.520 Hom.: 22038

Bravo AF: 0.599

Asia WGS AF: 0.624 AC: 2168 AN: 3478

EpiCase AF: 0.464

EpiControl AF: 0.465

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 44 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs364519; hg19: chr3-191100561; COSMIC: COSV66668267;