13-102729633-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146197.3(CCDC168):​c.21064G>A​(p.Ala7022Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,548,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

CCDC168
NM_001146197.3 missense

Scores

2
2
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
CCDC168 (HGNC:26851): (coiled-coil domain containing 168)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15192786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC168NM_001146197.3 linkc.21064G>A p.Ala7022Thr missense_variant Exon 4 of 4 ENST00000322527.4 NP_001139669.1 Q8NDH2
CCDC168XM_011521106.2 linkc.20944G>A p.Ala6982Thr missense_variant Exon 5 of 5 XP_011519408.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC168ENST00000322527.4 linkc.21064G>A p.Ala7022Thr missense_variant Exon 4 of 4 3 NM_001146197.3 ENSP00000320232.3 Q8NDH2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000259
AC:
4
AN:
154692
Hom.:
0
AF XY:
0.0000122
AC XY:
1
AN XY:
81728
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000120
Gnomad NFE exome
AF:
0.0000334
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000859
AC:
12
AN:
1396730
Hom.:
0
Cov.:
32
AF XY:
0.00000726
AC XY:
5
AN XY:
688874
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000610
Gnomad4 NFE exome
AF:
0.00000742
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.21064G>A (p.A7022T) alteration is located in exon 4 (coding exon 4) of the CCDC168 gene. This alteration results from a G to A substitution at nucleotide position 21064, causing the alanine (A) at amino acid position 7022 to be replaced by a threonine (T). 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
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
23
DANN
Pathogenic
1.0
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Benign
0.39
N
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.39
T
REVEL
Benign
0.084
Sift4G
Pathogenic
0.0
D
Vest4
0.13
MVP
0.088
ClinPred
0.74
D
GERP RS
4.5
gMVP
0.050

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

LitVar

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

Other links and lift over

dbSNP: rs867077480; hg19: chr13-103381983; API