Variant 2-62000929-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 15/21 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Variant links:

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]

COMMD1 links:

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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=0.21149993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMMD1	NM_152516.4 linkuse as main transcript	c.409C>G	p.Gln137Glu	missense_variant	2/3	ENST00000311832.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMMD1	ENST00000311832.6 linkuse as main transcript	c.409C>G	p.Gln137Glu	missense_variant	2/3	1	NM_152516.4	P1	Q8N668-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727214

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.081

Eigen

Benign

-0.12

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

M_CAP

Benign

0.0041

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.85

REVEL

Benign

0.11

Sift

Benign

0.23

Sift4G

Benign

0.55

Polyphen

0.010

Vest4

0.23

MutPred

0.49

Loss of MoRF binding (P = 0.0594);

MVP

0.69

MPC

0.86

ClinPred

0.67

GERP RS

5.0

Varity_R

0.31

gMVP

0.31

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over