chr8-27765231-T-G

Variant names:

• chr8-27765231-T-G
• rs762598226
• NM_018246.3:c.49A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018246.3(CCDC25):​c.49A>C​(p.Ile17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,350,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. I17V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: CCDC25 NM_018246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19817781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.49A>C	p.Ile17Leu	missense_variant	Exon 2 of 9	ENST00000356537.9	NP_060716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC25	ENST00000356537.9	c.49A>C	p.Ile17Leu	missense_variant	Exon 2 of 9	1	NM_018246.3	ENSP00000348933.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.41e-7 AC: 1 AN: 1350110 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 666334

African (AFR) AF: 0.0000329 AC: 1 AN: 30372

American (AMR) AF: 0.00 AC: 0 AN: 34796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23814

East Asian (EAS) AF: 0.00 AC: 0 AN: 36444

South Asian (SAS) AF: 0.00 AC: 0 AN: 77918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5358

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039124

Other (OTH) AF: 0.00 AC: 0 AN: 55284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;.
PhyloP100		1.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.23	N;.
REVEL	Benign	0.13
Sift	Benign	0.32	T;.
Sift4G	Benign	0.40	T;.
Polyphen		0.075	B;.
Vest4		0.47
MutPred		0.61		Loss of catalytic residue at I17 (P = 0.0492);Loss of catalytic residue at I17 (P = 0.0492);
MVP		0.25
MPC		0.51
ClinPred		0.26	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.70
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762598226; hg19: chr8-27622748;