9-136805395-C-T

Variant names:

• chr9-136805395-C-T
• NM_001039374.5:c.886C>T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001039374.5(CCDC183):​c.886C>T​(p.Gln296*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC183 NM_001039374.5 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.00

Genes affected

CCDC183 (HGNC:28236): (coiled-coil domain containing 183)

CCDC183-AS1 (HGNC:44105): (CCDC183 antisense RNA 1)

ENSG00000273066 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-136805395-C-T is Pathogenic according to our data. Variant chr9-136805395-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2691849.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC183	NM_001039374.5	c.886C>T	p.Gln296*	stop_gained	Exon 9 of 14	ENST00000338005.7	NP_001034463.4
CCDC183-AS1	NR_024580.1	n.918G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC183	ENST00000338005.7	c.886C>T	p.Gln296*	stop_gained	Exon 9 of 14	1	NM_001039374.5	ENSP00000338013.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

-

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A heterozygous nonsense variation in exon 9 of the CCDC183 gene that results in the generation of premature stop codon at position 296 (p.Gln296Ter) was detected. This variant has not been reported in the 1000 genomes and gnomAD databases.The in-silico predictions of the variant are damaging by SIFT, LRT, MutationTaster2, CADD and REVEL. The reference codon is conserved across species. Validation of the variant and parental segregation analysis by Sanger sequencing showed the variant to be present in the proband and absent in both parents, confirming de novo inheritance. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.78	D
Vest4		0.23
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139699847;