1-43995143-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152499.4(CCDC24):c.533G>A(p.Arg178Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,580,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R178S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

CCDC24
NM_152499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.951

Publications

2 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]

CCDC24 links:

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

SLC6A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020285279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC24	NM_152499.4 link	c.533G>A	p.Arg178Lys	missense_variant	Exon 6 of 9	ENST00000372318.8	NP_689712.1	Q8N4L8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC24	ENST00000372318.8 link	c.533G>A	p.Arg178Lys	missense_variant	Exon 6 of 9	1	NM_152499.4	ENSP00000361392.3		Q8N4L8-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000303

AC:

AN:

198002

AF XY:

0.0000284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000840

AC:

AN:

1428094

Hom.:

Cov.:

AF XY:

0.00000848

AC XY:

AN XY:

707324

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32742

American (AMR)

AF:

0.000198

AC:

AN:

40500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25528

East Asian (EAS)

AF:

0.00

AC:

AN:

37950

South Asian (SAS)

AF:

0.00

AC:

AN:

81486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4212

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095802

Other (OTH)

AF:

0.0000339

AC:

AN:

58964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000830

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.533G>A (p.R178K) alteration is located in exon 6 (coding exon 5) of the CCDC24 gene. This alteration results from a G to A substitution at nucleotide position 533, causing the arginine (R) at amino acid position 178 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

Benign

0.089

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0098

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PhyloP100

0.95

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.0090

Sift

Benign

0.32

T;.

Sift4G

Benign

0.15

T;T

Polyphen

0.093

B;.

Vest4

0.082

MVP

0.35

MPC

0.029

ClinPred

0.10

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-43995143-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over