9-136804593-T-C

Variant names:

• chr9-136804593-T-C
• NM_001039374.5:c.758T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039374.5(CCDC183):​c.758T>C​(p.Ile253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC183 NM_001039374.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

Genes affected

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

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

ENSG00000273066 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20804304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC183	NM_001039374.5	c.758T>C	p.Ile253Thr	missense_variant	Exon 7 of 14	ENST00000338005.7	NP_001034463.4
CCDC183-AS1	NR_024580.1	n.1720A>G		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.758T>C	p.Ile253Thr	missense_variant	Exon 7 of 14	1	NM_001039374.5	ENSP00000338013.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.758T>C (p.I253T) alteration is located in exon 7 (coding exon 7) of the CCDC183 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the isoleucine (I) at amino acid position 253 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	0.011
Eigen_PC	Benign	0.0033
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.089
Sift	Benign	0.058	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.87	P
Vest4		0.50
MutPred		0.33		Loss of stability (P = 0.008);
MVP		0.39
MPC		0.51
ClinPred		0.66	D
GERP RS		3.1
Varity_R		0.070
gMVP		0.082

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139699045;