NM_019044.5:c.683C>G

Variant names:

• chr2-117975255-G-C
• rs17512204
• NM_019044.5:c.683C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019044.5(CCDC93):​c.683C>G​(p.Pro228Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P228L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC93 NM_019044.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13291776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC93	NM_019044.5	MANE Select	c.683C>G	p.Pro228Arg	missense	Exon 9 of 24	NP_061917.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC93	ENST00000376300.7	TSL:1 MANE Select	c.683C>G	p.Pro228Arg	missense	Exon 9 of 24	ENSP00000365477.2
	CCDC93	ENST00000884940.1		c.683C>G	p.Pro228Arg	missense	Exon 9 of 25	ENSP00000554999.1
	CCDC93	ENST00000951763.1		c.701C>G	p.Pro234Arg	missense	Exon 10 of 25	ENSP00000621822.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.6
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.042
Sift	Benign	0.087	T
Sift4G	Benign	0.50	T
Polyphen		0.017	B
Vest4		0.28
MutPred		0.24		Gain of MoRF binding (P = 2e-04)
MVP		0.51
MPC		0.30
ClinPred		0.15	T
GERP RS		5.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.071
gMVP		0.25
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs17512204; hg19: chr2-118732831;