X-49163816-C-T

Variant names:

• chrX-49163816-C-T
• rs1228620860
• NM_024859.4:c.83C>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.83C>T​(p.Ala28Val) 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. 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. A28D) has been classified 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: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• 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=0.18490076).

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.83C>T	p.Ala28Val	missense	Exon 2 of 6	NP_079135.3	Q9H6Y5-1
	MAGIX	NM_001099681.2		c.83C>T	p.Ala28Val	missense	Exon 2 of 5	NP_001093151.2	A0A087WUY6
	MAGIX	NM_001099682.2		c.83C>T	p.Ala28Val	missense	Exon 2 of 5	NP_001093152.2	Q9H6Y5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGIX	ENST00000595224.6	TSL:5 MANE Select	c.83C>T	p.Ala28Val	missense	Exon 2 of 6	ENSP00000471299.1	Q9H6Y5-1
	MAGIX	ENST00000615626.4	TSL:1	c.83C>T	p.Ala28Val	missense	Exon 2 of 5	ENSP00000479023.1	A0A087WUY6
	MAGIX	ENST00000614074.4	TSL:1	c.83C>T	p.Ala28Val	missense	Exon 2 of 5	ENSP00000484729.1	A0A087X263

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18245 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: 0.00

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: 933944 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 293714

African (AFR) AF: 0.00 AC: 0 AN: 18824

American (AMR) AF: 0.00 AC: 0 AN: 9366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13532

East Asian (EAS) AF: 0.00 AC: 0 AN: 20781

South Asian (SAS) AF: 0.00 AC: 0 AN: 33453

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30729

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2409

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 766229

Other (OTH) AF: 0.00 AC: 0 AN: 38621

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.84	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.76	P
Vest4		0.15
MutPred		0.35		Loss of helix (P = 0.0795)
MVP		0.092
ClinPred		0.74	D
GERP RS		3.1
PromoterAI		0.015	Neutral
Varity_R		0.030
gMVP		0.19
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1228620860; hg19: chrX-49020154;