chrX-49165328-C-G

Variant names:

• chrX-49165328-C-G
• rs782394182
• NM_024859.4:c.646C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024859.4(MAGIX):​c.646C>G​(p.Pro216Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,176,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 60 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 55 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

Genes affected

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

ENSG00000279422 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.030400664).
• BS2: High Hemizygotes in GnomAd4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGIX	NM_024859.4	MANE Select	c.646C>G	p.Pro216Ala	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.469C>G	p.Pro157Ala	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.418C>G	p.Pro140Ala	missense	Exon 4 of 5	NP_001093151.2	A0A087WUY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGIX	ENST00000595224.6	TSL:5 MANE Select	c.646C>G	p.Pro216Ala	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.418C>G	p.Pro140Ala	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.418C>G	p.Pro140Ala	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes AF: 0.000170 AC: 19 AN: 111799 Hom.: 0 Cov.: 23

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: 0.000328

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000320

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000122 AC: 16 AN: 131462 AF XY: 0.0000561

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000469

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000963

Gnomad FIN exome AF: 0.000151

Gnomad NFE exome AF: 0.000217

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 144 AN: 1064719 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 55 AN XY: 340659

African (AFR) AF: 0.0000391 AC: 1 AN: 25565

American (AMR) AF: 0.0000334 AC: 1 AN: 29952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18346

East Asian (EAS) AF: 0.0000694 AC: 2 AN: 28830

South Asian (SAS) AF: 0.0000201 AC: 1 AN: 49768

European-Finnish (FIN) AF: 0.000129 AC: 5 AN: 38676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3963

European-Non Finnish (NFE) AF: 0.000158 AC: 130 AN: 824869

Other (OTH) AF: 0.0000894 AC: 4 AN: 44750

GnomAD4 genome AF: 0.000170 AC: 19 AN: 111799 Hom.: 0 Cov.: 23 AF XY: 0.000147 AC XY: 5 AN XY: 33971

African (AFR) AF: 0.00 AC: 0 AN: 30725

American (AMR) AF: 0.00 AC: 0 AN: 10567

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2701

European-Finnish (FIN) AF: 0.000328 AC: 2 AN: 6095

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000320 AC: 17 AN: 53081

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.000291 Hom.: 2

Bravo AF: 0.0000869

ExAC AF: 0.000161 AC: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.052
DANN	Benign	0.60
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.021
Sift	Benign	0.067	T
Sift4G	Benign	0.11	T
Polyphen		0.26	B
Vest4		0.084
MutPred		0.24		Gain of MoRF binding (P = 0.0311)
MVP		0.072
ClinPred		0.052	T
GERP RS		-4.4
Varity_R		0.017
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782394182; hg19: chrX-49021666;