20-32704876-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_053041.3(COMMD7):​c.365G>A​(p.Arg122Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,772 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

COMMD7
NM_053041.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.168
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053587526).
BP6
Variant 20-32704876-C-T is Benign according to our data. Variant chr20-32704876-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3268926.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COMMD7NM_053041.3 linkc.365G>A p.Arg122Gln missense_variant Exon 6 of 9 ENST00000278980.11 NP_444269.2 Q86VX2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COMMD7ENST00000278980.11 linkc.365G>A p.Arg122Gln missense_variant Exon 6 of 9 1 NM_053041.3 ENSP00000278980.6 Q86VX2-1
ENSG00000285382ENST00000646357.1 linkc.365G>A p.Arg122Gln missense_variant Exon 6 of 9 ENSP00000493768.1 A0A2R8Y455

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249504
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135366
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461772
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 26, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.2
DANN
Benign
0.74
DEOGEN2
Benign
0.054
.;.;T;.;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.76
T;T;T;T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.054
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.81
.;.;L;.;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.0
.;.;N;N;.
REVEL
Benign
0.065
Sift
Benign
0.33
.;.;T;T;.
Sift4G
Benign
0.17
.;.;T;T;.
Polyphen
0.0020, 0.0030
.;.;B;B;.
Vest4
0.17, 0.18
MutPred
0.46
Loss of MoRF binding (P = 0.0219);Loss of MoRF binding (P = 0.0219);Loss of MoRF binding (P = 0.0219);.;.;
MVP
0.16
MPC
0.23
ClinPred
0.059
T
GERP RS
-6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.020
gMVP
0.27

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

LitVar

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

Other links and lift over

dbSNP: rs770963512; hg19: chr20-31292678; API