1-43991961-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BP4

The NM_152499.4(CCDC24):​c.83T>C​(p.Leu28Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000914 in 1,531,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

CCDC24
NM_152499.4 missense

Scores

7
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

Publications

0 publications found
Variant links:
Genes affected
CCDC24 (HGNC:28688): (coiled-coil domain containing 24) Predicted to act upstream of or within blastocyst hatching. [provided by Alliance of Genome Resources, Apr 2022]
SLC6A9 (HGNC:11056): (solute carrier family 6 member 9) The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]
SLC6A9 Gene-Disease associations (from GenCC):
  • atypical glycine encephalopathy
    Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
  • infantile glycine encephalopathy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, M_CAP, PrimateAI, PROVEAN [when max_spliceai, Eigen, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.38119072).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC24NM_152499.4 linkc.83T>C p.Leu28Pro missense_variant Exon 2 of 9 ENST00000372318.8 NP_689712.1 Q8N4L8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC24ENST00000372318.8 linkc.83T>C p.Leu28Pro missense_variant Exon 2 of 9 1 NM_152499.4 ENSP00000361392.3 Q8N4L8-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151870
Hom.:
0
Cov.:
33
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:
0.000390
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
GnomAD2 exomes
AF:
0.0000564
AC:
8
AN:
141938
AF XY:
0.0000801
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000717
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000870
AC:
12
AN:
1379378
Hom.:
0
Cov.:
33
AF XY:
0.0000103
AC XY:
7
AN XY:
677400
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31174
American (AMR)
AF:
0.00
AC:
0
AN:
34204
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24154
East Asian (EAS)
AF:
0.000338
AC:
12
AN:
35496
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77630
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48378
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4722
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1066744
Other (OTH)
AF:
0.00
AC:
0
AN:
56876
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151986
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41494
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000391
AC:
2
AN:
5116
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4766
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67950
Other (OTH)
AF:
0.00
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 23, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.83T>C (p.L28P) alteration is located in exon 2 (coding exon 1) of the CCDC24 gene. This alteration results from a T to C substitution at nucleotide position 83, causing the leucine (L) at amino acid position 28 to be replaced by a proline (P). 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
0.85
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Benign
-0.083
Eigen_PC
Benign
0.039
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.73
T;T
M_CAP
Pathogenic
0.48
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.7
M;.
PhyloP100
4.4
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-6.3
D;.
REVEL
Uncertain
0.52
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.93
MutPred
0.56
Gain of loop (P = 0);Gain of loop (P = 0);
MVP
0.47
MPC
0.27
ClinPred
0.68
D
GERP RS
4.7
PromoterAI
0.039
Neutral
Varity_R
0.96
gMVP
0.89
Mutation Taster
=58/42
polymorphism

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

Other links and lift over

dbSNP: rs544917842; hg19: chr1-44457633; API