Variant 10-32451740-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395015.1(CCDC7):c.98C>G(p.Pro33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CCDC7
NM_001395015.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.984

Variant links:

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

CCDC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07038522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC7	NM_001395015.1 linkuse as main transcript	c.98C>G	p.Pro33Arg	missense_variant	2/44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2 linkuse as main transcript	c.98C>G	p.Pro33Arg	missense_variant	2/44	5	NM_001395015.1	ENSP00000491655	A2	Q96M83-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251338

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.98C>G (p.P33R) alteration is located in exon 2 (coding exon 1) of the CCDC7 gene. This alteration results from a C to G substitution at nucleotide position 98, causing the proline (P) at amino acid position 33 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

.;.;T;T;T;.

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

.;T;T;T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.070

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M;.;.;.;M

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.6

D;D;D;D;D;.

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D;D;D;D;.

Sift4G

Uncertain

0.024

D;D;D;D;D;.

Polyphen

0.98, 1.0

.;.;D;.;.;D

Vest4

0.50

MutPred

0.35

Loss of ubiquitination at K38 (P = 0.0236);Loss of ubiquitination at K38 (P = 0.0236);Loss of ubiquitination at K38 (P = 0.0236);Loss of ubiquitination at K38 (P = 0.0236);Loss of ubiquitination at K38 (P = 0.0236);Loss of ubiquitination at K38 (P = 0.0236);

MVP

0.59

MPC

0.36

ClinPred

0.16

GERP RS

3.3

Varity_R

0.10

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over