20-32728106-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_053041.3(COMMD7):c.121C>G(p.Leu41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COMMD7 NM_053041.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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]

ACMG classification

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
COMMD7	NM_053041.3	c.121C>G	p.Leu41Val	missense_variant	2/9	ENST00000278980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMMD7	ENST00000278980.11	c.121C>G	p.Leu41Val	missense_variant	2/9	1	NM_053041.3	P4
COMMD7	ENST00000446419.6	c.118C>G	p.Leu40Val	missense_variant	2/9	2		A1
COMMD7	ENST00000474815.2	c.121C>G	p.Leu41Val	missense_variant	2/7	5
COMMD7	ENST00000610160.1	c.*34C>G		3_prime_UTR_variant, NMD_transcript_variant	3/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.121C>G (p.L41V) alteration is located in exon 2 (coding exon 2) of the COMMD7 gene. This alteration results from a C to G substitution at nucleotide position 121, causing the leucine (L) at amino acid position 41 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.65	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
Polyphen		1.0	.;.;D;D;.
Vest4		0.69, 0.53
MutPred		0.77		Loss of catalytic residue at L41 (P = 0.0543);Loss of catalytic residue at L41 (P = 0.0543);Loss of catalytic residue at L41 (P = 0.0543);.;Loss of catalytic residue at L41 (P = 0.0543);
MVP		0.28
MPC		0.56
ClinPred		0.89	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.28
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-31315913;