dbSNP rs1212659047: COMMD7:p.Gln21Arg (chr20-32743330-T-C) – 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_053041.3(COMMD7):c.62A>G(p.Gln21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,588 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. 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. Q21P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

COMMD7
NM_053041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Publications

0 publications found

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 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=0.119015545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053041.3. 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
	COMMD7	NM_053041.3	MANE Select	c.62A>G	p.Gln21Arg	missense	Exon 1 of 9	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.62A>G	p.Gln21Arg	missense	Exon 1 of 9	NP_001092809.1	Q86VX2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD7	ENST00000278980.11	TSL:1 MANE Select	c.62A>G	p.Gln21Arg	missense	Exon 1 of 9	ENSP00000278980.6	Q86VX2-1
ENSG00000285382	ENST00000646357.1		c.62A>G	p.Gln21Arg	missense	Exon 1 of 9	ENSP00000493768.1	A0A2R8Y455
COMMD7	ENST00000855720.1		c.62A>G	p.Gln21Arg	missense	Exon 1 of 9	ENSP00000525779.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.39e-7

AC:

AN:

1353588

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28910

American (AMR)

AF:

0.00

AC:

AN:

34020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23834

East Asian (EAS)

AF:

0.00

AC:

AN:

32744

South Asian (SAS)

AF:

0.00

AC:

AN:

77836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3954

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1063608

Other (OTH)

AF:

0.00

AC:

AN:

56132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.016

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.31

REVEL

Benign

0.069

Sift

Benign

0.60

Sift4G

Benign

0.55

Polyphen

0.0020

Vest4

0.31

MutPred

0.46

Gain of catalytic residue at Q21 (P = 0.1288)

MVP

0.19

MPC

0.19

ClinPred

0.061

GERP RS

3.1

PromoterAI

0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.21

Mutation Taster

=88/12

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