rs782468533

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-49165298-C-A
• chrX-49165298-C-G
• chrX-49165298-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024859.4(MAGIX):​c.616C>A​(p.Arg206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000936 in 1,068,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. R206P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08795151).

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>A	p.Arg206Ser	missense	Exon 5 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.439C>A	p.Arg147Ser	missense	Exon 4 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.388C>A	p.Arg130Ser	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>A	p.Arg206Ser	missense	Exon 5 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.388C>A	p.Arg130Ser	missense	Exon 4 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.388C>A	p.Arg130Ser	missense	Exon 4 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.36e-7 AC: 1 AN: 1068558 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 346590

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

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

American (AMR) AF: 0.0000330 AC: 1 AN: 30278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18793

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: 0.00 AC: 0 AN: 827246

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.051
DANN	Benign	0.74
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.041
Sift	Benign	0.38	T
Sift4G	Benign	0.51	T
Polyphen		0.0070	B
Vest4		0.080
MutPred		0.49		Loss of MoRF binding (P = 0.0189)
MVP		0.048
ClinPred		0.052	T
GERP RS		-4.1
Varity_R		0.19
gMVP		0.66
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs782468533; hg19: chrX-49021636;