20-32704472-C-T

Variant names:

• chr20-32704472-C-T
• rs370081454
• NM_053041.3:c.445G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_053041.3(COMMD7):​c.445G>A​(p.Glu149Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000405 in 1,605,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: COMMD7 NM_053041.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 2 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.445G>A	p.Glu149Lys	missense	Exon 7 of 9	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.442G>A	p.Glu148Lys	missense	Exon 7 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.445G>A	p.Glu149Lys	missense	Exon 7 of 9	ENSP00000278980.6	Q86VX2-1
	ENSG00000285382	ENST00000646357.1		c.445G>A	p.Glu149Lys	missense	Exon 7 of 9	ENSP00000493768.1	A0A2R8Y455
	COMMD7	ENST00000855720.1		c.445G>A	p.Glu149Lys	missense	Exon 7 of 9	ENSP00000525779.1

Frequencies

GnomAD3 genomes AF: 0.0000407 AC: 6 AN: 147400 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000743

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000329 AC: 8 AN: 243478 AF XY: 0.0000302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000540

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1458330 Hom.: 0 Cov.: 32 AF XY: 0.0000400 AC XY: 29 AN XY: 725490

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 26002

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1110514

Other (OTH) AF: 0.0000498 AC: 3 AN: 60270

GnomAD4 genome AF: 0.0000407 AC: 6 AN: 147400 Hom.: 0 Cov.: 30 AF XY: 0.0000280 AC XY: 2 AN XY: 71386

African (AFR) AF: 0.0000252 AC: 1 AN: 39606

American (AMR) AF: 0.00 AC: 0 AN: 14492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000743 AC: 5 AN: 67326

Other (OTH) AF: 0.00 AC: 0 AN: 1968

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.000110

EpiControl AF: 0.00

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	Uncertain	0.40
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.088
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.66
MVP		0.38
MPC		0.68
ClinPred		0.81	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.50
Mutation Taster		=76/24	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: rs370081454; hg19: chr20-31292274; COSMIC: COSV54069843; COSMIC: COSV54069843;