X-49166311-C-T

Variant names:

• chrX-49166311-C-T
• rs1557098053
• NM_024859.4:c.917C>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.917C>T​(p.Pro306Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50
• 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=0.2534362).

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.917C>T	p.Pro306Leu	missense	Exon 6 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001395401.1		c.740C>T	p.Pro247Leu	missense	Exon 5 of 5	NP_001382330.1	Q9H6Y5-2
	MAGIX	NM_001099681.2		c.689C>T	p.Pro230Leu	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.917C>T	p.Pro306Leu	missense	Exon 6 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.689C>T	p.Pro230Leu	missense	Exon 5 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.674C>T	p.Pro225Leu	missense	Exon 5 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000814 AC: 1 AN: 122885 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1064797 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 346243

African (AFR) AF: 0.00 AC: 0 AN: 25432

American (AMR) AF: 0.00 AC: 0 AN: 29865

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18775

East Asian (EAS) AF: 0.00 AC: 0 AN: 27990

South Asian (SAS) AF: 0.00 AC: 0 AN: 50756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825527

Other (OTH) AF: 0.00 AC: 0 AN: 44780

GnomAD4 genome Cov.: 23

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Uncertain	0.63	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.34		Loss of glycosylation at P306 (P = 0.0854)
MVP		0.77
ClinPred		0.84	D
GERP RS		3.2
Varity_R		0.12
gMVP		0.63
Mutation Taster		=99/1	polymorphism

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: rs1557098053; hg19: chrX-49022650;