Variant chr1-43991966-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152499.4(CCDC24):c.88G>C(p.Glu30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,378,024 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: not found (cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CCDC24
NM_152499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2181195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC24	NM_152499.4 linkuse as main transcript	c.88G>C	p.Glu30Gln	missense_variant	2/9	ENST00000372318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC24	ENST00000372318.8 linkuse as main transcript	c.88G>C	p.Glu30Gln	missense_variant	2/9	1	NM_152499.4	P1	Q8N4L8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000710

AC:

AN:

140824

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74046

show subpopulations

Gnomad AFR exome

AF:

0.000120

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000653

AC:

AN:

1378024

Hom.:

Cov.:

AF XY:

0.00000444

AC XY:

AN XY:

676386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000751

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.88G>C (p.E30Q) alteration is located in exon 2 (coding exon 1) of the CCDC24 gene. This alteration results from a G to C substitution at nucleotide position 88, causing the glutamic acid (E) at amino acid position 30 to be replaced by a glutamine (Q). 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

0.37

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.095

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.91

D;D;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.17

Sift

Uncertain

0.021

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;.

Vest4

0.56

MutPred

0.16

Gain of MoRF binding (P = 0.0294);Gain of MoRF binding (P = 0.0294);

MVP

0.16

MPC

0.091

ClinPred

0.54

GERP RS

4.7

Varity_R

0.28

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over