Genetic Variant COMMD8:p.Gly30Asp (chr4-47460277-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_017845.5(COMMD8):c.89G>A(p.Gly30Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000305 in 1,608,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

COMMD8
NM_017845.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.37

Publications

4 publications found

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]

COMMD8 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017845.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD8	NM_017845.5	MANE Select	c.89G>A	p.Gly30Asp	missense	Exon 2 of 5	NP_060315.1	Q9NX08
	COMMD8	NM_001329668.2		c.89G>A	p.Gly30Asp	missense	Exon 2 of 5	NP_001316597.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD8	ENST00000381571.6	TSL:1 MANE Select	c.89G>A	p.Gly30Asp	missense	Exon 2 of 5	ENSP00000370984.4	Q9NX08
COMMD8	ENST00000952424.1		c.89G>A	p.Gly30Asp	missense	Exon 2 of 6	ENSP00000622483.1
COMMD8	ENST00000860334.1		c.89G>A	p.Gly30Asp	missense	Exon 2 of 5	ENSP00000530393.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000611

AC:

AN:

245624

AF XY:

0.0000452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456654

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33198

American (AMR)

AF:

0.000251

AC:

AN:

43842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39260

South Asian (SAS)

AF:

0.00

AC:

AN:

84942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000991

AC:

AN:

1110056

Other (OTH)

AF:

0.0000166

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.00164

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000144

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0057

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

PhyloP100

6.4

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Benign

0.045

Sift4G

Benign

0.089

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.58

gMVP

0.74

Mutation Taster

=64/36

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over