Genetic Variant COMMD9:p.Thr46Ser (chr11-36280753-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014186.4(COMMD9):c.136A>T(p.Thr46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,610,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

COMMD9
NM_014186.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1581648).

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.136A>T	p.Thr46Ser	missense	Exon 2 of 6	NP_054905.2	Q53FR9
COMMD9	NM_001307937.2		c.109A>T	p.Thr37Ser	missense	Exon 3 of 7	NP_001294866.1
COMMD9	NM_001307932.2		c.136A>T	p.Thr46Ser	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.136A>T	p.Thr46Ser	missense	Exon 2 of 6	ENSP00000263401.5	Q9P000-1
COMMD9	ENST00000877672.1		c.136A>T	p.Thr46Ser	missense	Exon 2 of 6	ENSP00000547731.1
COMMD9	ENST00000532705.1	TSL:2	c.136A>T	p.Thr46Ser	missense	Exon 2 of 5	ENSP00000435599.1	E9PJ95

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000108

AC:

AN:

250352

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000198

AC:

289

AN:

1458132

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

725486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

85834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000251

AC:

279

AN:

1109614

Other (OTH)

AF:

0.000166

AC:

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.000118

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

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

Benign

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

0.13

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

M_CAP

Benign

0.0069

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

1.3

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Uncertain

0.013

Sift4G

Benign

0.29

Polyphen

0.64

Vest4

0.33

MVP

0.16

MPC

0.48

ClinPred

0.17

GERP RS

5.9

Varity_R

0.48

gMVP

0.22

Mutation Taster

=71/29

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over