9-136804791-C-A

Variant names:

• chr9-136804791-C-A
• rs770637747
• NM_001039374.5:c.822C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039374.5(CCDC183):​c.822C>A​(p.Asn274Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC183 NM_001039374.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.76
• Publications: 0 publications found

Genes affected

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

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

ENSG00000273066 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05959308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039374.5. 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
	CCDC183	NM_001039374.5	MANE Select	c.822C>A	p.Asn274Lys	missense	Exon 8 of 14	NP_001034463.4	Q5T5S1-1
	CCDC183-AS1	NR_024580.1		n.1522G>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC183	ENST00000338005.7	TSL:1 MANE Select	c.822C>A	p.Asn274Lys	missense	Exon 8 of 14	ENSP00000338013.6	Q5T5S1-1
	CCDC183	ENST00000479371.5	TSL:1	n.820C>A		non_coding_transcript_exon	Exon 8 of 13	ENSP00000419222.1	G5E9W6
	CCDC183	ENST00000371682.7	TSL:5	n.860C>A		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461630 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.24
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-1.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.019
Sift	Benign	0.31	T
Sift4G	Uncertain	0.020	D
Polyphen		0.0010	B
Vest4		0.34
MutPred		0.22		Gain of ubiquitination at N274 (P = 0.0042)
MVP		0.048
MPC		0.19
ClinPred		0.092	T
GERP RS		-1.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.069
gMVP		0.060
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs770637747; hg19: chr9-139699243;