2-117941290-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019044.5(CCDC93):​c.1421G>T​(p.Arg474Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,980 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 (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

8
7
4

Clinical Significance

Uncertain significance no assertion criteria provided 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC93NM_019044.5 linkuse as main transcriptc.1421G>T p.Arg474Ile missense_variant 19/24 ENST00000376300.7 NP_061917.3
CCDC93XM_011511359.2 linkuse as main transcriptc.1418G>T p.Arg473Ile missense_variant 19/24 XP_011509661.2
CCDC93XM_011511361.1 linkuse as main transcriptc.1133G>T p.Arg378Ile missense_variant 18/23 XP_011509663.1
CCDC93XM_047444816.1 linkuse as main transcriptc.1022G>T p.Arg341Ile missense_variant 16/21 XP_047300772.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC93ENST00000376300.7 linkuse as main transcriptc.1421G>T p.Arg474Ile missense_variant 19/241 NM_019044.5 ENSP00000365477 P4
CCDC93ENST00000319432.9 linkuse as main transcriptc.1418G>T p.Arg473Ile missense_variant 19/245 ENSP00000324135 A1
CCDC93ENST00000466171.1 linkuse as main transcriptn.65G>T non_coding_transcript_exon_variant 2/43
CCDC93ENST00000437999.5 linkuse as main transcriptc.*61G>T 3_prime_UTR_variant, NMD_transcript_variant 6/113 ENSP00000392989

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460980
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726858
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CCDC93-related condition Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 06, 2024The CCDC93 c.1421G>T variant is predicted to result in the amino acid substitution p.Arg474Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.0
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-5.4
D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.86
MutPred
0.59
Loss of disorder (P = 0.0392);.;
MVP
0.87
MPC
1.1
ClinPred
0.97
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.68
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs775660660; hg19: chr2-118698866; API