Variant 19-11351941-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080503.3(CCDC159):c.458G>A(p.Arg153Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,604,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

CCDC159
NM_001080503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

CCDC159 (HGNC:26996): (coiled-coil domain containing 159)

CCDC159 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039595634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC159	NM_001080503.3 linkuse as main transcript	c.458G>A	p.Arg153Gln	missense_variant	6/11	ENST00000458408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC159	ENST00000458408.6 linkuse as main transcript	c.458G>A	p.Arg153Gln	missense_variant	6/11	5	NM_001080503.3	P1	P0C7I6-2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

234024

Hom.:

AF XY:

0.0000788

AC XY:

AN XY:

126886

show subpopulations

Gnomad AFR exome

AF:

0.0000716

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000379

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000702

AC:

102

AN:

1452938

Hom.:

Cov.:

AF XY:

0.0000817

AC XY:

AN XY:

722014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000301

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000910

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2023

The c.458G>A (p.R153Q) alteration is located in exon 6 (coding exon 6) of the CCDC159 gene. This alteration results from a G to A substitution at nucleotide position 458, causing the arginine (R) at amino acid position 153 to be replaced by a glutamine (Q). 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

Benign

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

.;N;.

REVEL

Benign

0.029

Sift

Benign

0.39

.;T;.

Sift4G

Benign

0.69

T;T;T

Vest4

0.25

MVP

0.16

MPC

0.13

ClinPred

0.017

GERP RS

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over