Variant 12-110884198-C-T 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_152591.3(CCDC63):c.1022C>T(p.Thr341Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,082 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 (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

CCDC63
NM_152591.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.957

Variant links:

Genes affected

CCDC63 (HGNC:26669): (coiled-coil domain containing 63) Predicted to be involved in cilium movement; outer dynein arm assembly; and spermatid development. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CCDC63 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=0.07006636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC63	NM_152591.3 linkuse as main transcript	c.1022C>T	p.Thr341Met	missense_variant	8/12	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000308208.10 linkuse as main transcript	c.1022C>T	p.Thr341Met	missense_variant	8/12	2	NM_152591.3	ENSP00000312399	P2	Q8NA47-1
CCDC63	ENST00000552694.1 linkuse as main transcript	c.785C>T	p.Thr262Met	missense_variant	6/10	1		ENSP00000450217
CCDC63	ENST00000545036.5 linkuse as main transcript	c.902C>T	p.Thr301Met	missense_variant	7/11	2		ENSP00000445881	A2	Q8NA47-2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251442

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000841

AC:

123

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000322

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000850

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000538

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Jun 03, 2022

The c.1022C>T (p.T341M) alteration is located in exon 8 (coding exon 7) of the CCDC63 gene. This alteration results from a C to T substitution at nucleotide position 1022, causing the threonine (T) at amino acid position 341 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

0.78

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.091

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.38

MVP

0.085

MPC

0.14

ClinPred

0.075

GERP RS

3.9

Varity_R

0.075

gMVP

0.66

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

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