dbSNP rs782394182: MAGIX:p.Pro216Thr (chrX-49165328-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024859.4(MAGIX):c.646C>A(p.Pro216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,176,568 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P216A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000075 ( 0 hom. 3 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

0 publications found

Variant links:

Genes affected

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

MAGIX links:

ENSG00000279422 (HGNC:):

ENSG00000279422 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04158199).

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.646C>A	p.Pro216Thr	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001395401.1		c.469C>A	p.Pro157Thr	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
MAGIX	NM_001099681.2		c.418C>A	p.Pro140Thr	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.646C>A	p.Pro216Thr	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
MAGIX	ENST00000615626.4	TSL:1	c.418C>A	p.Pro140Thr	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
MAGIX	ENST00000614074.4	TSL:1	c.418C>A	p.Pro140Thr	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes

AF:

0.0000805

AC:

AN:

111799

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

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:

0.00

GnomAD2 exomes

AF:

0.00000761

AC:

AN:

131462

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000118

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000751

AC:

AN:

1064717

Hom.:

Cov.:

AF XY:

0.00000881

AC XY:

AN XY:

340657

show subpopulations

African (AFR)

AF:

0.000235

AC:

AN:

25565

American (AMR)

AF:

0.00

AC:

AN:

29951

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18346

East Asian (EAS)

AF:

0.00

AC:

AN:

28830

South Asian (SAS)

AF:

0.00

AC:

AN:

49768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3963

European-Non Finnish (NFE)

AF:

0.00000242

AC:

AN:

824869

Other (OTH)

AF:

0.00

AC:

AN:

44749

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

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:

0.0000983

AC:

AN:

111851

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

34033

show subpopulations

African (AFR)

AF:

0.000357

AC:

AN:

30792

American (AMR)

AF:

0.00

AC:

AN:

10580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00

AC:

AN:

2693

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6095

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53075

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.064

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.51

M_CAP

Benign

0.0042

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Benign

0.012

Sift

Benign

0.49

Sift4G

Benign

0.088

Polyphen

0.023

Vest4

0.040

MutPred

0.25

Gain of phosphorylation at P216 (P = 0.0194)

MVP

0.072

ClinPred

0.021

GERP RS

-4.4

Varity_R

0.038

gMVP

0.45

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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