NM_018246.3:c.419G>T

Variant names:

• chr8-27748209-C-A
• rs145210673
• NM_018246.3:c.419G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018246.3(CCDC25):​c.419G>T​(p.Arg140Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC25 NM_018246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39924702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.419G>T	p.Arg140Leu	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.419G>T	p.Arg140Leu	missense_variant	Exon 7 of 9	1	NM_018246.3	ENSP00000348933.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		3.2
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.95	P;.
Vest4		0.55
MutPred		0.27		Loss of MoRF binding (P = 0.0252);.;
MVP		0.42
MPC		0.67
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.37
Mutation Taster		=65/35	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: rs145210673; hg19: chr8-27605726;