NM_152499.4:c.64C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152499.4(CCDC24):c.64C>T(p.Arg22Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,388,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CCDC24
NM_152499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.444

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]

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: Unknown, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05651191).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152499.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC24	NM_152499.4	MANE Select	c.64C>T	p.Arg22Cys	missense	Exon 2 of 9	NP_689712.1	Q8N4L8-1
CCDC24	NM_001349129.1		c.-160C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001336058.1
CCDC24	NM_001349128.1		c.64C>T	p.Arg22Cys	missense	Exon 1 of 8	NP_001336057.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC24	ENST00000372318.8	TSL:1 MANE Select	c.64C>T	p.Arg22Cys	missense	Exon 2 of 9	ENSP00000361392.3	Q8N4L8-1
CCDC24	ENST00000463846.5	TSL:1	n.64C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476322.1	V9GYM6
CCDC24	ENST00000490563.5	TSL:1	n.177C>T		non_coding_transcript_exon	Exon 2 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000271

AC:

AN:

147726

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000165

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:

0.00000432

AC:

AN:

1388412

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31444

American (AMR)

AF:

0.000142

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24732

East Asian (EAS)

AF:

0.00

AC:

AN:

35656

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5040

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071914

Other (OTH)

AF:

0.00

AC:

AN:

57304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.80

M_CAP

Benign

0.063

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.44

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.2

REVEL

Benign

0.034

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.014

Polyphen

0.10

Vest4

0.19

MutPred

0.37

Loss of MoRF binding (P = 0.0037)

MVP

0.24

MPC

0.045

ClinPred

0.20

GERP RS

2.6

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.21

gMVP

0.37

Mutation Taster

=93/7

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over