16-57447539-C-G

Variant names:

• chr16-57447539-C-G
• rs538303703
• NM_020312.4:c.34C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_020312.4(COQ9):​c.34C>G​(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000864 in 1,157,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: COQ9 NM_020312.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.154

Genes affected

COQ9 (HGNC:25302): (coenzyme Q9) This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.[provided by RefSeq, Sep 2010]

CIAPIN1 (HGNC:28050): (cytokine induced apoptosis inhibitor 1) CIAPIN1 is a cytokine-induced inhibitor of apoptosis with no relation to apoptosis regulatory molecules of the BCL2 (MIM 151430) or CASP (see MIM 147678) families. Expression of CIAPIN1 is dependent on growth factor stimulation (Shibayama et al., 2004 [PubMed 14970183]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19657424).
• BP6: Variant 16-57447539-C-G is Benign according to our data. Variant chr16-57447539-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 214242.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ9	NM_020312.4	c.34C>G	p.Arg12Gly	missense_variant	Exon 1 of 9	ENST00000262507.11	NP_064708.1
CIAPIN1	NM_020313.4	c.-253G>C		upstream_gene_variant		ENST00000394391.9	NP_064709.2
CIAPIN1	NM_001308347.2	c.-253G>C		upstream_gene_variant			NP_001295276.1
CIAPIN1	NM_001308358.2	c.-253G>C		upstream_gene_variant			NP_001295287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ9	ENST00000262507.11	c.34C>G	p.Arg12Gly	missense_variant	Exon 1 of 9	1	NM_020312.4	ENSP00000262507.5
CIAPIN1	ENST00000394391.9	c.-253G>C		upstream_gene_variant		1	NM_020313.4	ENSP00000377914.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.64e-7 AC: 1 AN: 1157842 Hom.: 0 Cov.: 32 AF XY: 0.00000179 AC XY: 1 AN XY: 558630

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: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 25, 2014

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.0083	T;T;T;T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.72	T;T;T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.68	T;T;T;T;T
Polyphen		0.92	P;.;.;.;.
Vest4		0.59
MutPred		0.42		Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);
MVP		0.27
MPC		0.21
ClinPred		0.32	T
GERP RS		2.6
Varity_R		0.094
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs538303703; hg19: chr16-57481451;