Variant 2-117941261-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019044.5(CCDC93):c.1450A>G(p.Lys484Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC93	NM_019044.5 linkuse as main transcript	c.1450A>G	p.Lys484Glu	missense_variant	19/24	ENST00000376300.7	NP_061917.3
CCDC93	XM_011511359.2 linkuse as main transcript	c.1447A>G	p.Lys483Glu	missense_variant	19/24		XP_011509661.2
CCDC93	XM_011511361.1 linkuse as main transcript	c.1162A>G	p.Lys388Glu	missense_variant	18/23		XP_011509663.1
CCDC93	XM_047444816.1 linkuse as main transcript	c.1051A>G	p.Lys351Glu	missense_variant	16/21		XP_047300772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.1450A>G	p.Lys484Glu	missense_variant	19/24	1	NM_019044.5	ENSP00000365477	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1447A>G	p.Lys483Glu	missense_variant	19/24	5		ENSP00000324135	A1
CCDC93	ENST00000466171.1 linkuse as main transcript	n.94A>G		non_coding_transcript_exon_variant	2/4	3
CCDC93	ENST00000437999.5 linkuse as main transcript	c.*90A>G		3_prime_UTR_variant, NMD_transcript_variant	6/11	3		ENSP00000392989

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251374

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 16, 2024

The c.1450A>G (p.K484E) alteration is located in exon 19 (coding exon 19) of the CCDC93 gene. This alteration results from a A to G substitution at nucleotide position 1450, causing the lysine (K) at amino acid position 484 to be replaced by a glutamic acid (E). 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

0.27

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.076

T;T

Polyphen

0.97

D;.

Vest4

0.78

MutPred

0.34

Loss of MoRF binding (P = 0.0053);.;

MVP

0.78

MPC

0.47

ClinPred

0.74

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.44

gMVP

0.54

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