Variant 2-117939031-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.1603G>A(p.Glu535Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,408,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense, splice_region

Scores

Splicing: ADA: 0.9539

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.35

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:

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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, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC93	NM_019044.5 linkuse as main transcript	c.1603G>A	p.Glu535Lys	missense_variant, splice_region_variant	20/24	ENST00000376300.7	NP_061917.3
CCDC93	XM_011511359.2 linkuse as main transcript	c.1600G>A	p.Glu534Lys	missense_variant, splice_region_variant	20/24		XP_011509661.2
CCDC93	XM_011511361.1 linkuse as main transcript	c.1315G>A	p.Glu439Lys	missense_variant, splice_region_variant	19/23		XP_011509663.1
CCDC93	XM_047444816.1 linkuse as main transcript	c.1204G>A	p.Glu402Lys	missense_variant, splice_region_variant	17/21		XP_047300772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.1603G>A	p.Glu535Lys	missense_variant, splice_region_variant	20/24	1	NM_019044.5	ENSP00000365477	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1600G>A	p.Glu534Lys	missense_variant, splice_region_variant	20/24	5		ENSP00000324135	A1
CCDC93	ENST00000466171.1 linkuse as main transcript	n.247G>A		splice_region_variant, non_coding_transcript_exon_variant	3/4	3
CCDC93	ENST00000437999.5 linkuse as main transcript	c.*243G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	7/11	3		ENSP00000392989

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000710

AC:

AN:

1408136

Hom.:

Cov.:

AF XY:

0.00000995

AC XY:

AN XY:

703464

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000845

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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.1603G>A (p.E535K) alteration is located in exon 20 (coding exon 20) of the CCDC93 gene. This alteration results from a G to A substitution at nucleotide position 1603, causing the glutamic acid (E) at amino acid position 535 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

0.93

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

-0.019

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.90

MutPred

0.55

Gain of ubiquitination at E535 (P = 0.0198);.;

MVP

0.87

MPC

1.0

ClinPred

1.0

GERP RS

5.7

Varity_R

0.86

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Pathogenic

0.82

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