Variant 2-117941212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_019044.5(CCDC93):c.1499G>A(p.Arg500Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,404 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC93	NM_019044.5 linkuse as main transcript	c.1499G>A	p.Arg500Lys	missense_variant	19/24	ENST00000376300.7
CCDC93	XM_011511359.2 linkuse as main transcript	c.1496G>A	p.Arg499Lys	missense_variant	19/24
CCDC93	XM_011511361.1 linkuse as main transcript	c.1211G>A	p.Arg404Lys	missense_variant	18/23
CCDC93	XM_047444816.1 linkuse as main transcript	c.1100G>A	p.Arg367Lys	missense_variant	16/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.1499G>A	p.Arg500Lys	missense_variant	19/24	1	NM_019044.5	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1496G>A	p.Arg499Lys	missense_variant	19/24	5		A1
CCDC93	ENST00000466171.1 linkuse as main transcript	n.143G>A		non_coding_transcript_exon_variant	2/4	3
CCDC93	ENST00000437999.5 linkuse as main transcript	c.*139G>A		3_prime_UTR_variant, NMD_transcript_variant	6/11	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251266

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.00000824

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

Jul 19, 2022

The c.1499G>A (p.R500K) alteration is located in exon 19 (coding exon 19) of the CCDC93 gene. This alteration results from a G to A substitution at nucleotide position 1499, causing the arginine (R) at amino acid position 500 to be replaced by a lysine (K). 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

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.23

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

0.043

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

1.0

D;.

Vest4

0.97

MutPred

0.69

Gain of methylation at R500 (P = 0.0056);.;

MVP

0.88

MPC

0.96

ClinPred

0.97

GERP RS

5.4

Varity_R

0.80

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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