Genetic Variant NM_018246.3:c.102G>T (chr8-27762433-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018246.3(CCDC25):c.102G>T(p.Trp34Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC25
NM_018246.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Publications

0 publications found

Variant links:

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]

CCDC25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.81

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018246.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC25	NM_018246.3	MANE Select	c.102G>T	p.Trp34Cys	missense	Exon 3 of 9	NP_060716.2	Q86WR0-1
CCDC25	NM_001304529.2		c.102G>T	p.Trp34Cys	missense	Exon 3 of 7	NP_001291458.1	G3V121
CCDC25	NM_001304532.2		c.-51G>T		5_prime_UTR	Exon 3 of 8	NP_001291461.1	Q86WR0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC25	ENST00000356537.9	TSL:1 MANE Select	c.102G>T	p.Trp34Cys	missense	Exon 3 of 9	ENSP00000348933.4	Q86WR0-1
CCDC25	ENST00000517979.1	TSL:1	n.*269G>T		non_coding_transcript_exon	Exon 4 of 8	ENSP00000428499.1	E5RI21
CCDC25	ENST00000520202.5	TSL:1	n.102G>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000428587.1	Q0VGD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111670

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.3

PhyloP100

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.79

MutPred

0.59

Loss of catalytic residue at W34 (P = 0.0069)

MVP

0.50

MPC

1.7

ClinPred

1.0

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.81

Mutation Taster

=20/80

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over