8-27748171-G-A

Variant names:

• chr8-27748171-G-A
• rs757755754
• NM_018246.3:c.457C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018246.3(CCDC25):​c.457C>T​(p.Arg153Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,612,578 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R153H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CCDC25 NM_018246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06385538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.457C>T	p.Arg153Cys	missense_variant	Exon 7 of 9	ENST00000356537.9	NP_060716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC25	ENST00000356537.9	c.457C>T	p.Arg153Cys	missense_variant	Exon 7 of 9	1	NM_018246.3	ENSP00000348933.4

Frequencies

GnomAD3 genomes AF: 0.0000530 AC: 8 AN: 151084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000718 AC: 18 AN: 250574 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461494 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39696

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111768

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.0000530 AC: 8 AN: 151084 Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3 AN XY: 73654

African (AFR) AF: 0.00 AC: 0 AN: 40994

American (AMR) AF: 0.00 AC: 0 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67856

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000824 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.457C>T (p.R153C) alteration is located in exon 7 (coding exon 7) of the CCDC25 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the arginine (R) at amino acid position 153 to be replaced by a cysteine (C). 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	0.38
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	0.051
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		4.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.046
Sift	Benign	0.10	T;T
Sift4G	Benign	0.084	T;T
Polyphen		0.0090	B;.
Vest4		0.49
MutPred		0.22		Loss of MoRF binding (P = 0.0323);.;
MVP		0.44
MPC		0.67
ClinPred		0.14	T
GERP RS		5.4
Varity_R		0.14
gMVP		0.27
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs757755754; hg19: chr8-27605688; COSMIC: COSV62958758;