Variant 2-117920356-G-A 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.1883C>T(p.Ala628Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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:

(HGNC:):

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=0.1740458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC93	NM_019044.5 linkuse as main transcript	c.1883C>T	p.Ala628Val	missense_variant	24/24	ENST00000376300.7	NP_061917.3
CCDC93	XM_011511359.2 linkuse as main transcript	c.1880C>T	p.Ala627Val	missense_variant	24/24		XP_011509661.2
CCDC93	XM_011511361.1 linkuse as main transcript	c.1595C>T	p.Ala532Val	missense_variant	23/23		XP_011509663.1
CCDC93	XM_047444816.1 linkuse as main transcript	c.1484C>T	p.Ala495Val	missense_variant	21/21		XP_047300772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.1883C>T	p.Ala628Val	missense_variant	24/24	1	NM_019044.5	ENSP00000365477	P4
	ENST00000434708.1 linkuse as main transcript	n.281+136G>A		intron_variant, non_coding_transcript_variant		1
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1880C>T	p.Ala627Val	missense_variant	24/24	5		ENSP00000324135	A1
CCDC93	ENST00000437999.5 linkuse as main transcript	c.*523C>T		3_prime_UTR_variant, NMD_transcript_variant	11/11	3		ENSP00000392989

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249834

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000548

AC:

AN:

1460438

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jan 16, 2024

The c.1883C>T (p.A628V) alteration is located in exon 24 (coding exon 24) of the CCDC93 gene. This alteration results from a C to T substitution at nucleotide position 1883, causing the alanine (A) at amino acid position 628 to be replaced by a valine (V). 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

0.083

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.4

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.067

T;T

Polyphen

0.56

P;.

Vest4

0.24

MutPred

0.27

Gain of methylation at K627 (P = 0.118);.;

MVP

0.70

MPC

0.29

ClinPred

0.51

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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