20-32704879-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_053041.3(COMMD7):c.362C>T(p.Ala121Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,613,906 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 0.000033 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
COMMD7
NM_053041.3 missense
NM_053041.3 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 5.54
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 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=0.07472044).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMMD7 | NM_053041.3 | c.362C>T | p.Ala121Val | missense_variant | 6/9 | ENST00000278980.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMMD7 | ENST00000278980.11 | c.362C>T | p.Ala121Val | missense_variant | 6/9 | 1 | NM_053041.3 | P4 | |
COMMD7 | ENST00000446419.6 | c.359C>T | p.Ala120Val | missense_variant | 6/9 | 2 | A1 | ||
COMMD7 | ENST00000474815.2 | c.392C>T | p.Ala131Val | missense_variant | 6/7 | 5 | |||
COMMD7 | ENST00000610160.1 | c.*275C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152088Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
5
AN:
152088
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000681 AC: 17AN: 249492Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135360
GnomAD3 exomes
AF:
AC:
17
AN:
249492
Hom.:
AF XY:
AC XY:
7
AN XY:
135360
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461700Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727164
GnomAD4 exome
AF:
AC:
11
AN:
1461700
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
727164
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 30 AF XY: 0.0000403 AC XY: 3AN XY: 74408
GnomAD4 genome
?
AF:
AC:
5
AN:
152206
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
74408
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
10
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 | Sep 13, 2023 | The c.362C>T (p.A121V) alteration is located in exon 6 (coding exon 6) of the COMMD7 gene. This alteration results from a C to T substitution at nucleotide position 362, causing the alanine (A) at amino acid position 121 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
0.14, 0.11
.;.;B;B;.
Vest4
0.31, 0.31
MutPred
Gain of MoRF binding (P = 0.0886);Gain of MoRF binding (P = 0.0886);Gain of MoRF binding (P = 0.0886);.;.;
MVP
0.25
MPC
0.19
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at