22-21634076-G-A

Variant names:

• chr22-21634076-G-A
• rs975545009
• NM_152612.3:c.127G>A

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.127G>A​(p.Gly43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G43R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC116 NM_152612.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• 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=0.2441844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC116	NM_152612.3	c.127G>A	p.Gly43Ser	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.127G>A	p.Gly43Ser	missense_variant	Exon 3 of 5	1	NM_152612.3	ENSP00000292779.3
CCDC116	ENST00000607942.5	c.127G>A	p.Gly43Ser	missense_variant	Exon 3 of 4	2		ENSP00000476296.1
CCDC116	ENST00000425975.1	c.325G>A	p.Gly109Ser	missense_variant	Exon 3 of 3	4		ENSP00000401637.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461560 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60368

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	0.12
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M
PhyloP100		0.30
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.5	.;D;D
REVEL	Benign	0.060
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.16	T;T;T
Vest4		0.20
MutPred		0.35		Gain of glycosylation at G43 (P = 0.005);.;Gain of glycosylation at G43 (P = 0.005);
MVP		0.36
MPC		0.44
ClinPred		0.86	D
GERP RS		2.0
Varity_R		0.48
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs975545009; hg19: chr22-21988365;