22-21634329-G-C

Variant names:

• chr22-21634329-G-C
• rs748163397
• NM_152612.3:c.380G>C

Variant summary

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

The NM_152612.3(CCDC116):​c.380G>C​(p.Arg127Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R127Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC116 NM_152612.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 1 publications found

Genes affected

CCDC116 (HGNC:26688): (coiled-coil domain containing 116) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC116	NM_152612.3	c.380G>C	p.Arg127Pro	missense_variant	Exon 3 of 5	ENST00000292779.4	NP_689825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC116	ENST00000292779.4	c.380G>C	p.Arg127Pro	missense_variant	Exon 3 of 5	1	NM_152612.3	ENSP00000292779.3
CCDC116	ENST00000607942.5	c.380G>C	p.Arg127Pro	missense_variant	Exon 3 of 4	2		ENSP00000476296.1
CCDC116	ENST00000425975.1	c.*120G>C		downstream_gene_variant		4		ENSP00000401637.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		1.1
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.9	.;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.53
MutPred		0.41		Loss of MoRF binding (P = 0.0044);Loss of MoRF binding (P = 0.0044);
MVP		0.35
MPC		0.90
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.89
gMVP		0.27
Mutation Taster		=79/21	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: rs748163397; hg19: chr22-21988618;