chr2-62000929-C-G

Variant names:

• chr2-62000929-C-G
• NM_152516.4:c.409C>G

Variant summary

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

The NM_152516.4(COMMD1):​c.409C>G​(p.Gln137Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COMMD1 NM_152516.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

COMMD1 (HGNC:23024): (copper metabolism domain containing 1) Enables several functions, including phosphatidylinositol-3,4-bisphosphate binding activity; phospholipid binding activity; and protein homodimerization activity. Involved in several processes, including Golgi to plasma membrane transport; negative regulation of protein localization to cell surface; and regulation of cellular protein metabolic process. Acts upstream of or within negative regulation of NF-kappaB transcription factor activity. Located in cytosol; endosome; and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21149993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152516.4. 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
	COMMD1	NM_152516.4	MANE Select	c.409C>G	p.Gln137Glu	missense	Exon 2 of 3	NP_689729.1	Q8N668-1
	COMMD1	NM_001321781.3		c.211C>G	p.Gln71Glu	missense	Exon 2 of 3	NP_001308710.1
	COMMD1	NM_001321782.3		c.211C>G	p.Gln71Glu	missense	Exon 2 of 3	NP_001308711.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD1	ENST00000311832.6	TSL:1 MANE Select	c.409C>G	p.Gln137Glu	missense	Exon 2 of 3	ENSP00000308236.5	Q8N668-1
	COMMD1	ENST00000471704.1	TSL:1	n.441C>G		non_coding_transcript_exon	Exon 2 of 2
	COMMD1	ENST00000897153.1		c.502C>G	p.Gln168Glu	missense	Exon 3 of 4	ENSP00000567212.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461800 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

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	0.078
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.11
Sift	Benign	0.23	T
Sift4G	Benign	0.55	T
Polyphen		0.010	B
Vest4		0.23
MutPred		0.49		Loss of MoRF binding (P = 0.0594)
MVP		0.69
MPC		0.86
ClinPred		0.67	D
GERP RS		5.0
PromoterAI		0.011	Neutral
Varity_R		0.31
gMVP		0.31
Mutation Taster		=87/13	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: chr2-62228064; COSMIC: COSV61273397; COSMIC: COSV61273397;