Genetic Variant CCDC157:p.Pro191Leu (chr22-30370477-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001017437.5(CCDC157):c.572C>T(p.Pro191Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,110 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.021 ( 109 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 115 hom. )

Consequence

CCDC157
NM_001017437.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

7 publications found

Variant links:

Genes affected

CCDC157 (HGNC:33854): (coiled-coil domain containing 157)

CCDC157 links:

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RNF215 links:

KIAA1656 (HGNC:):

KIAA1656 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.002074033).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC157	NM_001017437.5 link	c.572C>T	p.Pro191Leu	missense_variant	Exon 5 of 12	ENST00000338306.8	NP_001017437.3	Q569K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8 link	c.572C>T	p.Pro191Leu	missense_variant	Exon 5 of 12	5	NM_001017437.5	ENSP00000343087.3		Q569K6

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3242

AN:

152220

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00575

AC:

1445

AN:

251454

AF XY:

0.00441

show subpopulations

Gnomad AFR exome

AF:

0.0746

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00235

AC:

3431

AN:

1461772

Hom.:

115

Cov.:

AF XY:

0.00211

AC XY:

1534

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.0789

AC:

2643

AN:

33480

American (AMR)

AF:

0.00494

AC:

221

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000174

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000147

AC:

163

AN:

1112012

Other (OTH)

AF:

0.00586

AC:

354

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

247

495

742

990

1237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.0213

AC:

3243

AN:

152338

Hom.:

109

Cov.:

AF XY:

0.0207

AC XY:

1541

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0722

AC:

3003

AN:

41564

American (AMR)

AF:

0.0116

AC:

177

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68032

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

151

302

454

605

756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00931

Hom.:

Bravo

AF:

0.0252

ESP6500AA

AF:

0.0672

AC:

296

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00684

AC:

830

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;T;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.58

.;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;.;.

PhyloP100

1.6

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

N;N;D;D

REVEL

Benign

0.051

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D

Polyphen

0.18

B;B;.;.

Vest4

0.20

MVP

0.22

MPC

0.47

ClinPred

0.033

GERP RS

4.3

Varity_R

0.057

gMVP

0.42

Mutation Taster

=99/1

polymorphism (auto)

(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

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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