Genetic Variant COMMD7:p.Ala94Glu (chr20-32706721-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_053041.3(COMMD7):c.281C>A(p.Ala94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COMMD7
NM_053041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

Variant links:

Genes affected

COMMD7 (HGNC:16223): (COMM domain containing 7) Enables NF-kappaB binding activity. Involved in negative regulation of NF-kappaB transcription factor activity; negative regulation of transcription, DNA-templated; and tumor necrosis factor-mediated signaling pathway. Predicted to be located in cytoplasmic vesicle. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

COMMD7 links:

ENSG00000285382 (HGNC:):

ENSG00000285382 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=0.09394142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD7	NM_053041.3 link	c.281C>A	p.Ala94Glu	missense_variant	Exon 4 of 9	ENST00000278980.11	NP_444269.2	Q86VX2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD7	ENST00000278980.11 link	c.281C>A	p.Ala94Glu	missense_variant	Exon 4 of 9	1	NM_053041.3	ENSP00000278980.6		Q86VX2-1
ENSG00000285382	ENST00000646357.1 link	c.281C>A	p.Ala94Glu	missense_variant	Exon 4 of 9			ENSP00000493768.1		A0A2R8Y455

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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

AF:

0.00000658

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.8

DANN

Benign

0.25

DEOGEN2

Benign

0.014

.;.;T;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.64

T;T;T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.094

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.38

.;.;N;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

1.6

.;.;N;N;.

REVEL

Benign

0.10

Sift

Benign

1.0

.;.;T;T;.

Sift4G

Benign

1.0

.;.;T;T;.

Polyphen

0.0010, 0.0

.;.;B;B;.

Vest4

0.31, 0.31

MutPred

0.40

Gain of ubiquitination at K90 (P = 0.0371);Gain of ubiquitination at K90 (P = 0.0371);Gain of ubiquitination at K90 (P = 0.0371);.;.;

MVP

0.26

MPC

0.21

ClinPred

0.17

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over