Genetic Variant CCDC137:p.His127Gln (chr17-81670337-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199287.3(CCDC137):c.381C>G(p.His127Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,736 control chromosomes in the GnomAD database, including 38,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4833 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33256 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.126

Publications

28 publications found

Variant links:

Genes affected

CCDC137 (HGNC:33451): (coiled-coil domain containing 137) Enables RNA binding activity. Located in chromosome and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

CCDC137 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041407943).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3 link	c.381C>G	p.His127Gln	missense_variant	Exon 3 of 6	ENST00000329214.13	NP_954981.1	Q6PK04
CCDC137	XM_047435910.1 link	c.171C>G	p.His57Gln	missense_variant	Exon 3 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13 link	c.381C>G	p.His127Gln	missense_variant	Exon 3 of 6	1	NM_199287.3	ENSP00000329360.8		Q6PK04

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36861

AN:

152056

Hom.:

4814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.242

GnomAD2 exomes

AF:

0.199

AC:

49523

AN:

248654

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.210

AC:

306649

AN:

1461562

Hom.:

33256

Cov.:

AF XY:

0.207

AC XY:

150741

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.365

AC:

12233

AN:

33480

American (AMR)

AF:

0.138

AC:

6170

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4818

AN:

26136

East Asian (EAS)

AF:

0.258

AC:

10241

AN:

39694

South Asian (SAS)

AF:

0.153

AC:

13189

AN:

86254

European-Finnish (FIN)

AF:

0.195

AC:

10383

AN:

53224

Middle Eastern (MID)

AF:

0.237

AC:

1364

AN:

5766

European-Non Finnish (NFE)

AF:

0.211

AC:

235073

AN:

1111914

Other (OTH)

AF:

0.218

AC:

13178

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13363

26725

40088

53450

66813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8312

16624

24936

33248

41560

<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:

0.243

AC:

36921

AN:

152174

Hom.:

4833

Cov.:

AF XY:

0.238

AC XY:

17709

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.350

AC:

14534

AN:

41478

American (AMR)

AF:

0.189

AC:

2889

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3472

East Asian (EAS)

AF:

0.216

AC:

1118

AN:

5172

South Asian (SAS)

AF:

0.155

AC:

749

AN:

4820

European-Finnish (FIN)

AF:

0.189

AC:

2004

AN:

10598

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14181

AN:

68020

Other (OTH)

AF:

0.240

AC:

506

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1438

2876

4313

5751

7189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.213

Hom.:

1153

Bravo

AF:

0.250

TwinsUK

AF:

0.212

AC:

785

ALSPAC

AF:

0.213

AC:

820

ESP6500AA

AF:

0.336

AC:

1319

ESP6500EA

AF:

0.214

AC:

1782

ExAC

AF:

0.204

AC:

24613

Asia WGS

AF:

0.192

AC:

667

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.1

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.00071

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.21

.;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.5

N;.

PhyloP100

0.13

PrimateAI

Benign

0.25

PROVEAN

Benign

1.1

N;.

REVEL

Benign

0.036

Sift

Benign

1.0

T;.

Sift4G

Benign

0.76

T;T

Polyphen

0.0

B;.

Vest4

0.022

MutPred

0.081

Gain of helix (P = 0.062);.;

MPC

0.060

ClinPred

0.00019

GERP RS

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.15

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over