Variant 11-36280753-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 13/21 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

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:

COMMD9 (HGNC:):

COMMD9 links:

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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=0.1581648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMMD9	NM_014186.4 linkuse as main transcript	c.136A>T	p.Thr46Ser	missense_variant	2/6	ENST00000263401.10	NP_054905.2	Q9P000-1Q53FR9
COMMD9	NM_001307937.2 linkuse as main transcript	c.109A>T	p.Thr37Ser	missense_variant	3/7		NP_001294866.1	Q9P000Q53FR9
COMMD9	NM_001307932.2 linkuse as main transcript	c.136A>T	p.Thr46Ser	missense_variant	2/5		NP_001294861.1	Q53FR9E9PJ95
COMMD9	NM_001101653.2 linkuse as main transcript	c.52-2137A>T		intron_variant			NP_001095123.1	Q53FR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMMD9	ENST00000263401.10 linkuse as main transcript	c.136A>T	p.Thr46Ser	missense_variant	2/6	1	NM_014186.4	ENSP00000263401.5		Q9P000-1

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

GnomAD3 exomes

AF:

0.000108

AC:

AN:

250352

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135354

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 SAS 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

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:

0.000251

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000118

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.136A>T (p.T46S) alteration is located in exon 2 (coding exon 2) of the COMMD9 gene. This alteration results from a A to T substitution at nucleotide position 136, causing the threonine (T) at amino acid position 46 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.013

D;D

Sift4G

Benign

0.29

T;T

Polyphen

0.64

P;.

Vest4

0.33

MVP

0.16

MPC

0.48

ClinPred

0.17

GERP RS

5.9

Varity_R

0.48

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over