Genetic Variant CCDC24:p.Ile97Ile (chr1-43992376-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_152499.4(CCDC24):c.291C>T(p.Ile97Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,614,182 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 29 hom. )

Consequence

CCDC24
NM_152499.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.143

Publications

4 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 -6 ACMG points.

BP6

Variant 1-43992376-C-T is Benign according to our data. Variant chr1-43992376-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638764.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC24	NM_152499.4 link	c.291C>T	p.Ile97Ile	synonymous_variant	Exon 3 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.291C>T	p.Ile97Ile	synonymous_variant	Exon 3 of 9	1	NM_152499.4	ENSP00000361392.3		Q8N4L8-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

594

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00650

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00403

AC:

1012

AN:

250908

AF XY:

0.00410

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00497

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00610

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00577

AC:

8433

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

4135

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33480

American (AMR)

AF:

0.00157

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00520

AC:

136

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00335

AC:

289

AN:

86256

European-Finnish (FIN)

AF:

0.00313

AC:

167

AN:

53408

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00665

AC:

7392

AN:

1111976

Other (OTH)

AF:

0.00503

AC:

304

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

496

992

1488

1984

2480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152346

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41574

American (AMR)

AF:

0.00183

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00248

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00650

AC:

442

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.00362

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00640

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CCDC24: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.28

Position offset: 11

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

Publications

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1-43992376-C-T

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