10-22318820-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012071.4(COMMD3):āc.426T>Gā(p.His142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,008 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000037 ( 0 hom. )
Consequence
COMMD3
NM_012071.4 missense
NM_012071.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 1.59
Genes affected
COMMD3 (HGNC:23332): (COMM domain containing 3) Predicted to be involved in sodium ion transport. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMMD3 | NM_012071.4 | c.426T>G | p.His142Gln | missense_variant | 6/8 | ENST00000376836.8 | |
COMMD3-BMI1 | NM_001204062.2 | c.351-139T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMMD3 | ENST00000376836.8 | c.426T>G | p.His142Gln | missense_variant | 6/8 | 1 | NM_012071.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251284Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135834
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727128
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74498
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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 | Feb 22, 2023 | The c.426T>G (p.H142Q) alteration is located in exon 6 (coding exon 6) of the COMMD3 gene. This alteration results from a T to G substitution at nucleotide position 426, causing the histidine (H) at amino acid position 142 to be replaced by a glutamine (Q). 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
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0874);.;
MVP
MPC
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
DS_AG_spliceai
Position offset: -14
DS_DG_spliceai
Position offset: 42
Find out detailed SpliceAI scores and Pangolin per-transcript scores at