Genetic Variant MAGIX:p.Arg29Trp (chrX-49163818-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001395401.1(MAGIX):c.-166C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,047,861 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000043 ( 0 hom. 1 hem. )

Consequence

MAGIX
NM_001395401.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

Publications

0 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18830553).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395401.1. 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.85C>T	p.Arg29Trp	missense	Exon 2 of 6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001395401.1		c.-166C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001382330.1	Q9H6Y5-2
MAGIX	NM_001099681.2		c.85C>T	p.Arg29Trp	missense	Exon 2 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.85C>T	p.Arg29Trp	missense	Exon 2 of 6	ENSP00000471299.1	Q9H6Y5-1
MAGIX	ENST00000615626.4	TSL:1	c.85C>T	p.Arg29Trp	missense	Exon 2 of 5	ENSP00000479023.1	A0A087WUY6
MAGIX	ENST00000614074.4	TSL:1	c.85C>T	p.Arg29Trp	missense	Exon 2 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes

AF:

0.0000888

AC:

AN:

112632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000653

GnomAD4 exome

AF:

0.00000428

AC:

AN:

935229

Hom.:

Cov.:

AF XY:

0.00000340

AC XY:

AN XY:

294347

show subpopulations

African (AFR)

AF:

0.000159

AC:

AN:

18844

American (AMR)

AF:

0.00

AC:

AN:

9490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13614

East Asian (EAS)

AF:

0.00

AC:

AN:

20798

South Asian (SAS)

AF:

0.00

AC:

AN:

33708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30991

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2430

European-Non Finnish (NFE)

AF:

0.00000130

AC:

AN:

766662

Other (OTH)

AF:

0.00

AC:

AN:

38692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000888

AC:

AN:

112632

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

34890

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

31109

American (AMR)

AF:

0.00

AC:

AN:

10783

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3529

South Asian (SAS)

AF:

0.00

AC:

AN:

2808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6215

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53091

Other (OTH)

AF:

0.000653

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000756

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

0.21

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.10

PrimateAI

Pathogenic

0.87

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.15

MutPred

0.51

Loss of methylation at R29 (P = 0.0262)

MVP

0.17

ClinPred

0.92

GERP RS

0.36

PromoterAI

-0.15

Neutral

(source)

Varity_R

0.12

gMVP

0.51

Mutation Taster

=300/0

polymorphism

(source)

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

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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