X-49165298-C-G

Variant names:

• chrX-49165298-C-G
• rs782468533
• NM_024859.4:c.616C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024859.4(MAGIX):​c.616C>G​(p.Arg206Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,180,852 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts 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. R206P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000030 (0 hom. 12 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 12 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.616C>G	p.Arg206Gly	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.439C>G	p.Arg147Gly	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.388C>G	p.Arg130Gly	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.616C>G	p.Arg206Gly	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.388C>G	p.Arg130Gly	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.388C>G	p.Arg130Gly	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112288 Hom.: 0 Cov.: 24

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

GnomAD4 exome AF: 0.0000299 AC: 32 AN: 1068564 Hom.: 0 Cov.: 31 AF XY: 0.0000346 AC XY: 12 AN XY: 346594

African (AFR) AF: 0.00 AC: 0 AN: 25610

American (AMR) AF: 0.00 AC: 0 AN: 30279

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18794

East Asian (EAS) AF: 0.00 AC: 0 AN: 28368

South Asian (SAS) AF: 0.00 AC: 0 AN: 50653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38537

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4077

European-Non Finnish (NFE) AF: 0.0000387 AC: 32 AN: 827250

Other (OTH) AF: 0.00 AC: 0 AN: 44996

GnomAD4 genome AF: 0.00000891 AC: 1 AN: 112288 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34460

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30873

American (AMR) AF: 0.00 AC: 0 AN: 10629

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 2752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6177

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53188

Other (OTH) AF: 0.00 AC: 0 AN: 1509

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.9
DANN	Benign	0.85
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-1.0
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.097
Sift	Uncertain	0.010	D
Sift4G	Benign	0.16	T
Polyphen		0.43	B
Vest4		0.17
MutPred		0.52		Loss of MoRF binding (P = 0.0156)
MVP		0.12
ClinPred		0.31	T
GERP RS		-4.1
Varity_R		0.19
gMVP		0.79
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 0

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

Other links and lift over

dbSNP: rs782468533; hg19: chrX-49021636;