rs373091485

Variant names:

• chr20-32703419-A-G
• rs373091485
• NM_053041.3:c.566T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_053041.3(COMMD7):​c.566T>C​(p.Met189Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M189V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: COMMD7 NM_053041.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD7	NM_053041.3	MANE Select	c.566T>C	p.Met189Thr	missense	Exon 9 of 9	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.563T>C	p.Met188Thr	missense	Exon 9 of 9	NP_001092809.1	Q86VX2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD7	ENST00000278980.11	TSL:1 MANE Select	c.566T>C	p.Met189Thr	missense	Exon 9 of 9	ENSP00000278980.6	Q86VX2-1
	ENSG00000285382	ENST00000646357.1		c.526+604T>C		intron	N/A	ENSP00000493768.1	A0A2R8Y455
	COMMD7	ENST00000855720.1		c.644T>C	p.Met215Thr	missense	Exon 9 of 9	ENSP00000525779.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000481 AC: 12 AN: 249226 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461790 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727210

African (AFR) AF: 0.000598 AC: 20 AN: 33468

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74452

African (AFR) AF: 0.000650 AC: 27 AN: 41552

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.89
MVP		0.40
MPC		0.76
ClinPred		0.49	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.70
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs373091485; hg19: chr20-31291221;