Genetic Variant MAGIX:p.Pro216Ser (chrX-49165328-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024859.4(MAGIX):c.646C>T(p.Pro216Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000939 in 1,064,716 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/25 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: not found (cov: 23)

Exomes 𝑓: 9.4e-7 ( 0 hom. 1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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>T	p.Pro216Ser	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001395401.1		c.469C>T	p.Pro157Ser	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
MAGIX	NM_001099681.2		c.418C>T	p.Pro140Ser	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>T	p.Pro216Ser	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
MAGIX	ENST00000615626.4	TSL:1	c.418C>T	p.Pro140Ser	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
MAGIX	ENST00000614074.4	TSL:1	c.418C>T	p.Pro140Ser	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.39e-7

AC:

AN:

1064716

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

340656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25565

American (AMR)

AF:

0.00

AC:

AN:

29952

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:

0.00000121

AC:

AN:

824866

Other (OTH)

AF:

0.00

AC:

AN:

44750

Age Distribution

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.064

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.54

M_CAP

Benign

0.0026

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.2

REVEL

Benign

0.0080

Sift

Benign

0.35

Sift4G

Benign

0.29

Polyphen

0.010

Vest4

0.031

MutPred

0.25

Gain of phosphorylation at P216 (P = 0.0219)

MVP

0.072

ClinPred

0.078

GERP RS

-4.4

Varity_R

0.022

gMVP

0.42

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.72

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.72

Position offset: -6

DS_DL_spliceai

0.35

Position offset: 33

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over