chr20-32743330-T-C

Variant names:

• chr20-32743330-T-C
• NM_053041.3:c.62A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: COMMD7 NM_053041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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]

ENSG00000285382 (HGNC:):

ACMG classification

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=0.119015545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD7	NM_053041.3	c.62A>G	p.Gln21Arg	missense_variant	Exon 1 of 9	ENST00000278980.11	NP_444269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD7	ENST00000278980.11	c.62A>G	p.Gln21Arg	missense_variant	Exon 1 of 9	1	NM_053041.3	ENSP00000278980.6
ENSG00000285382	ENST00000646357.1	c.62A>G	p.Gln21Arg	missense_variant	Exon 1 of 9			ENSP00000493768.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353588 Hom.: 0 Cov.: 34 AF XY: 0.00000150 AC XY: 1 AN XY: 667692

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.40e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Benign	0.56
DEOGEN2	Benign	0.016	.;.;T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	.;.;N;N;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.31	.;.;N;N;.
REVEL	Benign	0.069
Sift	Benign	0.60	.;.;T;T;.
Sift4G	Benign	0.55	.;.;T;T;.
Polyphen		0.0020, 0.039	.;.;B;B;.
Vest4		0.31, 0.27
MutPred		0.46		Gain of catalytic residue at Q21 (P = 0.1288);Gain of catalytic residue at Q21 (P = 0.1288);Gain of catalytic residue at Q21 (P = 0.1288);Gain of catalytic residue at Q21 (P = 0.1288);Gain of catalytic residue at Q21 (P = 0.1288);
MVP		0.19
MPC		0.19
ClinPred		0.061	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-31331136;