Genetic Variant MAGIX:p.Arg206Cys (chrX-49165298-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_024859.4(MAGIX):c.616C>T(p.Arg206Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,180,852 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.000020 ( 0 hom. 5 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

Publications

2 publications found

Variant links:

Genes affected

MAGIX (HGNC:30006): (MAGI family member, X-linked)

MAGIX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26924768).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGIX	NM_024859.4	MANE Select	c.616C>T	p.Arg206Cys	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001395401.1		c.439C>T	p.Arg147Cys	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
MAGIX	NM_001099681.2		c.388C>T	p.Arg130Cys	missense	Exon 4 of 5	NP_001093151.2	A0A087WUY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGIX	ENST00000595224.6	TSL:5 MANE Select	c.616C>T	p.Arg206Cys	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
MAGIX	ENST00000615626.4	TSL:1	c.388C>T	p.Arg130Cys	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
MAGIX	ENST00000614074.4	TSL:1	c.388C>T	p.Arg130Cys	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes

AF:

0.0000802

AC:

AN:

112288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

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:

0.0000752

Gnomad OTH

AF:

0.00199

GnomAD2 exomes

AF:

0.00000763

AC:

AN:

131041

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1068564

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

346594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25610

American (AMR)

AF:

0.0000330

AC:

AN:

30279

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18794

East Asian (EAS)

AF:

0.0000353

AC:

AN:

28368

South Asian (SAS)

AF:

0.00

AC:

AN:

50653

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38537

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.0000169

AC:

AN:

827250

Other (OTH)

AF:

0.000111

AC:

AN:

44996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000802

AC:

AN:

112288

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34460

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30873

American (AMR)

AF:

0.0000941

AC:

AN:

10629

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3580

South Asian (SAS)

AF:

0.00

AC:

AN:

2752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6177

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53188

Other (OTH)

AF:

0.00199

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000342

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.91

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.087

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.74

M_CAP

Benign

0.020

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.0

PhyloP100

-1.0

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.096

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.022

Polyphen

0.025

Vest4

0.076

MutPred

0.54

Loss of MoRF binding (P = 0.0031)

MVP

0.20

ClinPred

0.48

GERP RS

-4.1

Varity_R

0.11

gMVP

0.74

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over