chrX-49164888-C-T

Variant names:

• chrX-49164888-C-T
• rs782749138
• NM_024859.4:c.305C>T

Variant summary

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

The NM_024859.4(MAGIX):​c.305C>T​(p.Ala102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,210,727 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 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 0.000089 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.00013 (0 hom. 43 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.08
• Publications: 1 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.031441152).
• BS2: High Hemizygotes in GnomAd4 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.305C>T	p.Ala102Val	missense	Exon 4 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.128C>T	p.Ala43Val	missense	Exon 3 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.279+99C>T		intron	N/A	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.305C>T	p.Ala102Val	missense	Exon 4 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.279+99C>T		intron	N/A	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.279+99C>T		intron	N/A	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes AF: 0.0000886 AC: 10 AN: 112804 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: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.000654

GnomAD2 exomes AF: 0.0000826 AC: 15 AN: 181573 AF XY: 0.0000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.000133 AC: 146 AN: 1097923 Hom.: 0 Cov.: 31 AF XY: 0.000118 AC XY: 43 AN XY: 363355

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.0000284 AC: 1 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.000222 AC: 9 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000157 AC: 132 AN: 841853

Other (OTH) AF: 0.0000868 AC: 4 AN: 46078

GnomAD4 genome AF: 0.0000886 AC: 10 AN: 112804 Hom.: 0 Cov.: 24 AF XY: 0.0000572 AC XY: 2 AN XY: 34952

African (AFR) AF: 0.00 AC: 0 AN: 31068

American (AMR) AF: 0.00 AC: 0 AN: 10741

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3593

South Asian (SAS) AF: 0.00 AC: 0 AN: 2760

European-Finnish (FIN) AF: 0.000160 AC: 1 AN: 6262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53274

Other (OTH) AF: 0.000654 AC: 1 AN: 1529

Alfa AF: 0.000182 Hom.: 2

Bravo AF: 0.0000642

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

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	0.081
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0060
DANN	Benign	0.78
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-2.1
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.065	T
Polyphen		0.56	P
Vest4		0.071
MVP		0.099
ClinPred		0.027	T
GERP RS		-6.4
PromoterAI		0.020	Neutral
Varity_R		0.019
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs782749138; hg19: chrX-49021226;