chr20-32704445-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_053041.3(COMMD7):c.472T>G(p.Leu158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,611,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
COMMD7
NM_053041.3 missense
NM_053041.3 missense
Scores
6
7
Clinical Significance
Conservation
PhyloP100: 2.61
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.288917).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMMD7 | NM_053041.3 | c.472T>G | p.Leu158Val | missense_variant | 7/9 | ENST00000278980.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMMD7 | ENST00000278980.11 | c.472T>G | p.Leu158Val | missense_variant | 7/9 | 1 | NM_053041.3 | P4 | |
COMMD7 | ENST00000446419.6 | c.469T>G | p.Leu157Val | missense_variant | 7/9 | 2 | A1 | ||
COMMD7 | ENST00000610160.1 | c.*385T>G | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 2 | ||||
COMMD7 | ENST00000474815.2 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152028Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000114 AC: 28AN: 246398Hom.: 0 AF XY: 0.0000823 AC XY: 11AN XY: 133710
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GnomAD4 exome AF: 0.000217 AC: 317AN: 1459224Hom.: 0 Cov.: 32 AF XY: 0.000200 AC XY: 145AN XY: 725828
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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 | Apr 12, 2023 | The c.472T>G (p.L158V) alteration is located in exon 7 (coding exon 7) of the COMMD7 gene. This alteration results from a T to G substitution at nucleotide position 472, causing the leucine (L) at amino acid position 158 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
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
0.96, 0.99
.;.;D;D
Vest4
0.48, 0.48
MVP
0.21
MPC
0.62
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at