Variant 5-42779458-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 ENST00000361970.10(CCDC152):c.263G>A(p.Gly88Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000646 in 1,471,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 1 hom. )

Consequence

CCDC152
ENST00000361970.10 missense, splice_region

Scores

Splicing: ADA: 0.001115

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

CCDC152 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=0.010000348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC152	NM_001134848.2 linkuse as main transcript	c.263G>A	p.Gly88Asp	missense_variant, splice_region_variant	5/9	ENST00000361970.10	NP_001128320.1
CCDC152	XM_047416584.1 linkuse as main transcript	c.326G>A	p.Gly109Asp	missense_variant, splice_region_variant	5/9		XP_047272540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC152	ENST00000361970.10 linkuse as main transcript	c.263G>A	p.Gly88Asp	missense_variant, splice_region_variant	5/9	1	NM_001134848.2	ENSP00000354888	P1	Q4G0S7-1
CCDC152	ENST00000388827.4 linkuse as main transcript	c.262+9793G>A		intron_variant		2		ENSP00000373479		Q4G0S7-2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000916

AC:

AN:

152782

Hom.:

AF XY:

0.0000617

AC XY:

AN XY:

80994

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000659

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.000696

GnomAD4 exome

AF:

0.0000515

AC:

AN:

1319624

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

655172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000673

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000369

Gnomad4 SAS exome

AF:

0.0000260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.91e-7

Gnomad4 OTH exome

AF:

0.000904

GnomAD4 genome

AF:

0.000178

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.000435

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000230

ExAC

AF:

0.000164

AC:

Asia WGS

AF:

0.00145

AC:

AN:

3474

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 29, 2024

The c.263G>A (p.G88D) alteration is located in exon 5 (coding exon 4) of the CCDC152 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the glycine (G) at amino acid position 88 to be replaced by an aspartic acid (D). 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

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.5

DANN

Benign

0.34

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.54

M_CAP

Benign

0.011

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

MutationTaster

Benign

0.64

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

0.070

REVEL

Benign

0.037

Sift

Benign

0.91

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.16

MVP

0.040

ClinPred

0.0054

GERP RS

-0.18

Varity_R

0.053

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.070

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