Genetic Variant NM_001039374.5:c.710G>A (chr9-136804545-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039374.5(CCDC183):c.710G>A(p.Arg237Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R237G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

CCDC183
NM_001039374.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.386

Publications

1 publications found

Variant links:

Genes affected

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

CCDC183 links:

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

CCDC183-AS1 links:

ENSG00000273066 (HGNC:):

ENSG00000273066 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014949322).

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.710G>A	p.Arg237Gln	missense	Exon 7 of 14	NP_001034463.4	Q5T5S1-1
	CCDC183-AS1	NR_024580.1		n.1768C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC183	ENST00000338005.7	TSL:1 MANE Select	c.710G>A	p.Arg237Gln	missense	Exon 7 of 14	ENSP00000338013.6	Q5T5S1-1
CCDC183	ENST00000479371.5	TSL:1	n.708G>A		non_coding_transcript_exon	Exon 7 of 13	ENSP00000419222.1	G5E9W6
CCDC183	ENST00000371682.7	TSL:5	n.748G>A		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000219

AC:

AN:

246302

AF XY:

0.000231

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000452

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000958

AC:

140

AN:

1461214

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

726878

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.000932

AC:

AN:

39696

South Asian (SAS)

AF:

0.000487

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1111938

Other (OTH)

AF:

0.000199

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00251

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000252

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000232

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.76

M_CAP

Benign

0.0067

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

0.39

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

REVEL

Benign

0.045

Sift

Benign

0.17

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.37

MVP

0.30

MPC

0.35

ClinPred

0.060

GERP RS

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over