chr9-136804599-C-A

Variant names:

• chr9-136804599-C-A
• rs557045264
• NM_001039374.5:c.764C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039374.5(CCDC183):​c.764C>A​(p.Thr255Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,440 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T255R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC183 NM_001039374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18093795).

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.764C>A	p.Thr255Lys	missense	Exon 7 of 14	NP_001034463.4	Q5T5S1-1
	CCDC183-AS1	NR_024580.1		n.1714G>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.764C>A	p.Thr255Lys	missense	Exon 7 of 14	ENSP00000338013.6	Q5T5S1-1
	CCDC183	ENST00000479371.5	TSL:1	n.762C>A		non_coding_transcript_exon	Exon 7 of 13	ENSP00000419222.1	G5E9W6
	CCDC183	ENST00000371682.7	TSL:5	n.802C>A		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461440 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.074
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.059
Sift	Benign	0.18	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.96	D
Vest4		0.41
MutPred		0.28		Gain of methylation at T255 (P = 0.0163)
MVP		0.31
MPC		0.53
ClinPred		0.57	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs557045264; hg19: chr9-139699051;