Genetic Variant COMMD7:p.Val164Ile (chr20-32704059-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053041.3(COMMD7):c.490G>A(p.Val164Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

COMMD7
NM_053041.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Variant links:

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]

COMMD7 links:

ENSG00000285382 (HGNC:):

ENSG00000285382 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10142985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD7	NM_053041.3 link	c.490G>A	p.Val164Ile	missense_variant	Exon 8 of 9	ENST00000278980.11	NP_444269.2	Q86VX2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD7	ENST00000278980.11 link	c.490G>A	p.Val164Ile	missense_variant	Exon 8 of 9	1	NM_053041.3	ENSP00000278980.6		Q86VX2-1
ENSG00000285382	ENST00000646357.1 link	c.490G>A	p.Val164Ile	missense_variant	Exon 8 of 9			ENSP00000493768.1		A0A2R8Y455

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000817

AC:

AN:

244776

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1453958

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722650

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.00000542

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000491

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.490G>A (p.V164I) alteration is located in exon 8 (coding exon 8) of the COMMD7 gene. This alteration results from a G to A substitution at nucleotide position 490, causing the valine (V) at amino acid position 164 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.025

.;.;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

0.14

.;.;N;N

REVEL

Benign

0.063

Sift

Benign

0.30

.;.;T;T

Sift4G

Benign

0.46

.;.;T;T

Polyphen

0.046, 0.037

.;.;B;B

Vest4

0.18, 0.18

MutPred

0.55

Loss of methylation at K165 (P = 0.1346);Loss of methylation at K165 (P = 0.1346);Loss of methylation at K165 (P = 0.1346);.;

MVP

0.18

MPC

0.16

ClinPred

0.14

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.029

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over