Variant 2-117939106-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.1528G>A(p.Ala510Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,018 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25898588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC93	NM_019044.5 linkuse as main transcript	c.1528G>A	p.Ala510Thr	missense_variant	20/24	ENST00000376300.7	NP_061917.3
CCDC93	XM_011511359.2 linkuse as main transcript	c.1525G>A	p.Ala509Thr	missense_variant	20/24		XP_011509661.2
CCDC93	XM_011511361.1 linkuse as main transcript	c.1240G>A	p.Ala414Thr	missense_variant	19/23		XP_011509663.1
CCDC93	XM_047444816.1 linkuse as main transcript	c.1129G>A	p.Ala377Thr	missense_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.1528G>A	p.Ala510Thr	missense_variant	20/24	1	NM_019044.5	ENSP00000365477	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1525G>A	p.Ala509Thr	missense_variant	20/24	5		ENSP00000324135	A1
CCDC93	ENST00000466171.1 linkuse as main transcript	n.172G>A		non_coding_transcript_exon_variant	3/4	3
CCDC93	ENST00000437999.5 linkuse as main transcript	c.*168G>A		3_prime_UTR_variant, NMD_transcript_variant	7/11	3		ENSP00000392989

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443018

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718970

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 17, 2021

The c.1528G>A (p.A510T) 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 1528, causing the alanine (A) at amino acid position 510 to be replaced by a threonine (T). 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

0.080

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.13

Sift

Benign

0.083

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.49

P;.

Vest4

0.39

MutPred

0.23

Gain of methylation at K513 (P = 0.0904);.;

MVP

0.71

MPC

0.35

ClinPred

0.96

GERP RS

5.7

Varity_R

0.29

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over