Variant chr13-102730037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001146197.3(CCDC168):c.20660C>T(p.Ala6887Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,551,432 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

CCDC168
NM_001146197.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.382

Variant links:

Genes affected

CCDC168 (HGNC:26851): (coiled-coil domain containing 168)

CCDC168 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053850412).

BP6

Variant 13-102730037-G-A is Benign according to our data. Variant chr13-102730037-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2331546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC168	NM_001146197.3 linkuse as main transcript	c.20660C>T	p.Ala6887Val	missense_variant	4/4	ENST00000322527.4
CCDC168	XM_011521106.2 linkuse as main transcript	c.20540C>T	p.Ala6847Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC168	ENST00000322527.4 linkuse as main transcript	c.20660C>T	p.Ala6887Val	missense_variant	4/4	3	NM_001146197.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000511

AC:

AN:

156578

Hom.:

AF XY:

0.000410

AC XY:

AN XY:

82834

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000826

Gnomad OTH exome

AF:

0.00250

GnomAD4 exome

AF:

0.000129

AC:

180

AN:

1399208

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

690112

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000556

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000388

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000782

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.047

DANN

Benign

0.54

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0039

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

REVEL

Benign

0.024

Sift4G

Benign

0.29

Vest4

0.082

MVP

0.014

ClinPred

0.0042

GERP RS

-0.17

gMVP

0.0018

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

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