chr8-27748095-C-T

Position:

• chr8-27748095-C-T

Variant summary

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

The NM_018246.3(CCDC25):​c.533G>A​(p.Arg178Lys) 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: 33)
• Consequence: CCDC25 NM_018246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.451

Genes affected

CCDC25 (HGNC:25591): (coiled-coil domain containing 25) Enables DNA binding activity. Involved in positive regulation of cell motility. Located in endomembrane system. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253875 (HGNC:):

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=0.031522095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.533G>A	p.Arg178Lys	missense_variant	7/9	ENST00000356537.9	NP_060716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC25	ENST00000356537.9	c.533G>A	p.Arg178Lys	missense_variant	7/9	1	NM_018246.3	ENSP00000348933.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.533G>A (p.R178K) alteration is located in exon 7 (coding exon 7) of the CCDC25 gene. This alteration results from a G to A substitution at nucleotide position 533, causing the arginine (R) at amino acid position 178 to be replaced by a lysine (K). 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	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.2
DANN	Benign	0.74
DEOGEN2	Benign	0.0035	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.0	N;N
REVEL	Benign	0.22
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.16
MutPred		0.16		Gain of ubiquitination at R178 (P = 0.0238);.;
MVP		0.24
MPC		0.49
ClinPred		0.10	T
GERP RS		1.1
Varity_R		0.060
gMVP		0.033

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: rs1803665718; hg19: chr8-27605612;