chrX-49166248-C-G

Variant names:

• chrX-49166248-C-G
• rs782164364
• NM_024859.4:c.854C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024859.4(MAGIX):​c.854C>G​(p.Pro285Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,200,812 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000074 (0 hom. 2 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.359
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08831784).
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.854C>G	p.Pro285Arg	missense	Exon 6 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.677C>G	p.Pro226Arg	missense	Exon 5 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.626C>G	p.Pro209Arg	missense	Exon 5 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.854C>G	p.Pro285Arg	missense	Exon 6 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.626C>G	p.Pro209Arg	missense	Exon 5 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.611C>G	p.Pro204Arg	missense	Exon 5 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112815 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000322

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

GnomAD4 exome AF: 0.00000735 AC: 8 AN: 1087945 Hom.: 0 Cov.: 31 AF XY: 0.00000563 AC XY: 2 AN XY: 355555

African (AFR) AF: 0.0000764 AC: 2 AN: 26179

American (AMR) AF: 0.00 AC: 0 AN: 33921

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19195

East Asian (EAS) AF: 0.00 AC: 0 AN: 29677

South Asian (SAS) AF: 0.00 AC: 0 AN: 52683

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39593

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837046

Other (OTH) AF: 0.000131 AC: 6 AN: 45649

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 112867 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 35019

African (AFR) AF: 0.0000642 AC: 2 AN: 31167

American (AMR) AF: 0.00 AC: 0 AN: 10785

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2662

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.00 AC: 0 AN: 2791

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53218

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.077
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.36
PrimateAI	Benign	0.33	T
Sift4G	Uncertain	0.058	T
Polyphen		0.89	P
Vest4		0.035
MutPred		0.16		Loss of catalytic residue at P284 (P = 0.0191)
MVP		0.095
ClinPred		0.80	D
GERP RS		0.48
Varity_R		0.048
gMVP		0.25
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs782164364; hg19: chrX-49022587;