Variant 2-117973990-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_019044.5(CCDC93):c.806G>A(p.Arg269His) variant causes a missense change. The variant allele was found at a frequency of 0.0000946 in 1,606,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

CCDC93 (HGNC:25611): (coiled-coil domain containing 93) Involved in Golgi to plasma membrane transport and endocytic recycling. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

CCDC93 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=0.22716665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC93	NM_019044.5 linkuse as main transcript	c.806G>A	p.Arg269His	missense_variant	11/24	ENST00000376300.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.806G>A	p.Arg269His	missense_variant	11/24	1	NM_019044.5	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.803G>A	p.Arg268His	missense_variant	11/24	5		A1
CCDC93	ENST00000460781.1 linkuse as main transcript	n.370G>A		non_coding_transcript_exon_variant	7/10	3

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000500

AC:

AN:

240022

Hom.:

AF XY:

0.0000464

AC XY:

AN XY:

129408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000976

AC:

142

AN:

1454282

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

723004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000970

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000577

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

Dec 28, 2022

The c.806G>A (p.R269H) alteration is located in exon 11 (coding exon 11) of the CCDC93 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.51

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.079

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.090

T;T

Polyphen

1.0

D;.

Vest4

0.48

MVP

0.52

MPC

0.93

ClinPred

0.40

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.30

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