chr20-32704046-T-C

Variant names:

• chr20-32704046-T-C
• NM_053041.3:c.503A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053041.3(COMMD7):​c.503A>G​(p.Asn168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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: 0.931
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11347121).

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.503A>G	p.Asn168Ser	missense	Exon 8 of 9	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.500A>G	p.Asn167Ser	missense	Exon 8 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.503A>G	p.Asn168Ser	missense	Exon 8 of 9	ENSP00000278980.6	Q86VX2-1
	ENSG00000285382	ENST00000646357.1		c.503A>G	p.Asn168Ser	missense	Exon 8 of 9	ENSP00000493768.1	A0A2R8Y455
	COMMD7	ENST00000855718.1		c.578A>G	p.Asn193Ser	missense	Exon 9 of 10	ENSP00000525777.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458214 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724886

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110182

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 32

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	Benign	0.064
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.84	L
PhyloP100		0.93
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.068
Sift	Benign	0.20	T
Sift4G	Benign	0.28	T
Polyphen		0.0060	B
Vest4		0.14
MutPred		0.29		Gain of disorder (P = 0.1699)
MVP		0.24
MPC		0.16
ClinPred		0.18	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.022
gMVP		0.17
Mutation Taster		=84/16	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

hg19: chr20-31291848;