chr19-17943613-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136203.2(CCDC124):​c.570C>A​(p.Asn190Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95
Variant links:
Genes affected
CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC124NM_001136203.2 linkuse as main transcriptc.570C>A p.Asn190Lys missense_variant 5/5 ENST00000445755.7 NP_001129675.1 Q96CT7A0A024R7M8
CCDC124NM_138442.4 linkuse as main transcriptc.570C>A p.Asn190Lys missense_variant 5/5 NP_612451.1 Q96CT7A0A024R7M8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC124ENST00000445755.7 linkuse as main transcriptc.570C>A p.Asn190Lys missense_variant 5/52 NM_001136203.2 ENSP00000408730.1 Q96CT7
CCDC124ENST00000597436.5 linkuse as main transcriptc.570C>A p.Asn190Lys missense_variant 5/51 ENSP00000471455.1 Q96CT7

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000576
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:
0.000478
GnomAD3 exomes
AF:
0.0000843
AC:
21
AN:
249252
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135484
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00110
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000713
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1460694
Hom.:
0
Cov.:
34
AF XY:
0.0000372
AC XY:
27
AN XY:
726662
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.000689
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000743
AC:
9
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsSep 01, 2021The c.570C>A (p.N190K) alteration is located in exon 5 (coding exon 4) of the CCDC124 gene. This alteration results from a C to A substitution at nucleotide position 570, causing the asparagine (N) at amino acid position 190 to be replaced by a lysine (K). 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
Pathogenic
0.93
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Uncertain
2.9
M;M
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.9
D;.
REVEL
Benign
0.27
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.042
D;D
Polyphen
0.99
D;D
Vest4
0.58
MutPred
0.55
Gain of MoRF binding (P = 0.037);Gain of MoRF binding (P = 0.037);
MVP
0.69
MPC
1.1
ClinPred
0.77
D
GERP RS
3.7
Varity_R
0.72
gMVP
0.54

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.

Other links and lift over

dbSNP: rs146510396; hg19: chr19-18054422; API