Genetic Variant COMMD9:p.Val24Ile (chr11-36280819-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014186.4(COMMD9):c.70G>A(p.Val24Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,435,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V24L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COMMD9
NM_014186.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88

Publications

2 publications found

Variant links:

Genes affected

COMMD9 (HGNC:25014): (COMM domain containing 9) Predicted to be involved in sodium ion transport. Predicted to act upstream of or within cholesterol homeostasis. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COMMD9 links:

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ACMG classification

Classification was made for transcript

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=0.23923174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014186.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD9	NM_014186.4	MANE Select	c.70G>A	p.Val24Ile	missense	Exon 2 of 6	NP_054905.2	Q53FR9
COMMD9	NM_001307937.2		c.43G>A	p.Val15Ile	missense	Exon 3 of 7	NP_001294866.1
COMMD9	NM_001307932.2		c.70G>A	p.Val24Ile	missense	Exon 2 of 5	NP_001294861.1	E9PJ95

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD9	ENST00000263401.10	TSL:1 MANE Select	c.70G>A	p.Val24Ile	missense	Exon 2 of 6	ENSP00000263401.5	Q9P000-1
COMMD9	ENST00000877672.1		c.70G>A	p.Val24Ile	missense	Exon 2 of 6	ENSP00000547731.1
COMMD9	ENST00000532705.1	TSL:2	c.70G>A	p.Val24Ile	missense	Exon 2 of 5	ENSP00000435599.1	E9PJ95

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1435878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713002

show subpopulations

African (AFR)

AF:

0.0000618

AC:

AN:

32340

American (AMR)

AF:

0.00

AC:

AN:

40654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25228

East Asian (EAS)

AF:

0.00

AC:

AN:

39158

South Asian (SAS)

AF:

0.00

AC:

AN:

82642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098342

Other (OTH)

AF:

0.00

AC:

AN:

59068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

0.066

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

M_CAP

Benign

0.0099

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

3.9

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.45

REVEL

Benign

0.12

Sift

Benign

0.070

Sift4G

Uncertain

0.028

Polyphen

0.0030

Vest4

0.28

MutPred

0.59

Loss of ubiquitination at K21 (P = 0.0768)

MVP

0.12

MPC

0.24

ClinPred

0.65

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.24

gMVP

0.28

Mutation Taster

=66/34

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

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