1-43996126-C-T

Position:

• chr1-43996126-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152499.4(CCDC24):​c.890C>T​(p.Pro297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC24 NM_152499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.378

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04104811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC24	NM_152499.4	c.890C>T	p.Pro297Leu	missense_variant	9/9	ENST00000372318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC24	ENST00000372318.8	c.890C>T	p.Pro297Leu	missense_variant	9/9	1	NM_152499.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.890C>T (p.P297L) alteration is located in exon 9 (coding exon 8) of the CCDC24 gene. This alteration results from a C to T substitution at nucleotide position 890, causing the proline (P) at amino acid position 297 to be replaced by a leucine (L). 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	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.2
DANN	Benign	0.50
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.031
Sift	Benign	0.59	T
Sift4G	Benign	0.13	T
Polyphen		0.017	B
Vest4		0.041
MutPred		0.087		Loss of loop (P = 0.0128);
MVP		0.11
MPC		0.030
ClinPred		0.031	T
GERP RS		2.7
Varity_R		0.030
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44461798;