chr1-43991966-G-C

Variant names:

• chr1-43991966-G-C
• rs1333965019
• NM_152499.4:c.88G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CCDC24	NM_152499.4	c.88G>C	p.Glu30Gln	missense_variant	Exon 2 of 9	ENST00000372318.8	NP_689712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC24	ENST00000372318.8	c.88G>C	p.Glu30Gln	missense_variant	Exon 2 of 9	1	NM_152499.4	ENSP00000361392.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000710 AC: 1 AN: 140824 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74046

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: 9 AN: 1378024 Hom.: 0 Cov.: 33 AF XY: 0.00000444 AC XY: 3 AN XY: 676386

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.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.72	T
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	D
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

Other links and lift over

dbSNP: rs1333965019; hg19: chr1-44457638;