chr22-21634182-C-G

Variant names:

• chr22-21634182-C-G
• rs1930668403
• NM_152612.3:c.233C>G

Variant summary

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

The NM_152612.3(CCDC116):​c.233C>G​(p.Thr78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. T78I) 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: 0.929
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19231269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC116	NM_152612.3	c.233C>G	p.Thr78Ser	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.233C>G	p.Thr78Ser	missense_variant	Exon 3 of 5	1	NM_152612.3	ENSP00000292779.3
CCDC116	ENST00000607942.5	c.233C>G	p.Thr78Ser	missense_variant	Exon 3 of 4	2		ENSP00000476296.1
CCDC116	ENST00000425975.1	c.431C>G	p.Thr144Ser	missense_variant	Exon 3 of 3	4		ENSP00000401637.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
PhyloP100		0.93
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.2	.;D;D
REVEL	Benign	0.020
Sift	Uncertain	0.020	.;D;D
Sift4G	Benign	0.067	T;D;T
Vest4		0.15
MutPred		0.22		Gain of disorder (P = 0.0489);.;Gain of disorder (P = 0.0489);
MVP		0.27
MPC		0.50
ClinPred		0.94	D
GERP RS		2.2
Varity_R		0.13
gMVP		0.078
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1930668403; hg19: chr22-21988471;