4-47463636-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017845.5(COMMD8):​c.16G>A​(p.Gly6Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

COMMD8
NM_017845.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81
Variant links:
Genes affected
COMMD8 (HGNC:26036): (COMM domain containing 8) The protein encoded by this gene binds coiled-coil domain-containing protein 22 (CCDC22), and this complex can regulate the turnover of I-kappa-B and the activation of NF-kappa-B. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22612402).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COMMD8NM_017845.5 linkc.16G>A p.Gly6Arg missense_variant Exon 1 of 5 ENST00000381571.6 NP_060315.1 Q9NX08

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COMMD8ENST00000381571.6 linkc.16G>A p.Gly6Arg missense_variant Exon 1 of 5 1 NM_017845.5 ENSP00000370984.4 Q9NX08
COMMD8ENST00000509220.1 linkn.30G>A non_coding_transcript_exon_variant Exon 1 of 2 2
ENSG00000282904ENST00000634784.2 linkn.47C>T non_coding_transcript_exon_variant Exon 1 of 3 3
ENSG00000282904ENST00000635489.1 linkn.-148C>T upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1396926
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
688930
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.16G>A (p.G6R) alteration is located in exon 1 (coding exon 1) of the COMMD8 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.012
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.0034
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.095
Sift
Benign
0.064
T
Sift4G
Benign
0.61
T
Polyphen
0.96
D
Vest4
0.31
MutPred
0.33
Gain of solvent accessibility (P = 0.019);
MVP
0.37
MPC
0.16
ClinPred
0.73
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.20
gMVP
0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-47465653; COSMIC: COSV67500306; COSMIC: COSV67500306; API