1-43993948-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152499.4(CCDC24):​c.481G>A​(p.Val161Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V161L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CCDC24
NM_152499.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28092057).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC24NM_152499.4 linkc.481G>A p.Val161Met missense_variant Exon 5 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.481G>A p.Val161Met missense_variant Exon 5 of 9 1 NM_152499.4 ENSP00000361392.3 Q8N4L8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.481G>A (p.V161M) alteration is located in exon 5 (coding exon 4) of the CCDC24 gene. This alteration results from a G to A substitution at nucleotide position 481, causing the valine (V) at amino acid position 161 to be replaced by a methionine (M). 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
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.85
D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.8
M;.
PhyloP100
3.4
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N;.
REVEL
Benign
0.21
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;.
Vest4
0.56
MutPred
0.18
Gain of disorder (P = 0.0855);.;
MVP
0.16
MPC
0.13
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.19
gMVP
0.51
Mutation Taster
=87/13
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

hg19: chr1-44459620; API