Genetic Variant NM_024859.4:c.875C>T (chrX-49166269-C-T) – 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.875C>T(p.Pro292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,194,708 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 9 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.882

Publications

1 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05843997).

BS2

High Hemizygotes in GnomAdExome4 at 9 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.875C>T	p.Pro292Leu	missense	Exon 6 of 6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001395401.1		c.698C>T	p.Pro233Leu	missense	Exon 5 of 5	NP_001382330.1	Q9H6Y5-2
MAGIX	NM_001099681.2		c.647C>T	p.Pro216Leu	missense	Exon 5 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.875C>T	p.Pro292Leu	missense	Exon 6 of 6	ENSP00000471299.1	Q9H6Y5-1
MAGIX	ENST00000615626.4	TSL:1	c.647C>T	p.Pro216Leu	missense	Exon 5 of 5	ENSP00000479023.1	A0A087WUY6
MAGIX	ENST00000614074.4	TSL:1	c.632C>T	p.Pro211Leu	missense	Exon 5 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes

AF:

0.00000886

AC:

AN:

112907

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000688

AC:

AN:

145401

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1081801

Hom.:

Cov.:

AF XY:

0.0000256

AC XY:

AN XY:

352221

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26002

American (AMR)

AF:

0.00

AC:

AN:

32934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19079

East Asian (EAS)

AF:

0.00

AC:

AN:

29267

South Asian (SAS)

AF:

0.00

AC:

AN:

52098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3943

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

833931

Other (OTH)

AF:

0.0000440

AC:

AN:

45451

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000886

AC:

AN:

112907

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35057

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31137

American (AMR)

AF:

0.00

AC:

AN:

10801

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2797

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53241

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000378

ExAC

AF:

0.0000254

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

0.092

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.5

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

M_CAP

Benign

0.0071

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.88

PrimateAI

Benign

0.45

Sift4G

Benign

0.61

Polyphen

0.0040

Vest4

0.057

MutPred

0.19

Loss of relative solvent accessibility (P = 0.0676)

MVP

0.18

ClinPred

0.053

GERP RS

2.6

Varity_R

0.040

gMVP

0.24

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