X-49163798-C-G

Variant names:

• chrX-49163798-C-G
• rs1194432565
• NM_024859.4:c.65C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024859.4(MAGIX):​c.65C>G​(p.Pro22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 935,748 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000027 (0 hom. 8 hem.)
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.36

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056930482).
• BP6: Variant X-49163798-C-G is Benign according to our data. Variant chrX-49163798-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3122298.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-49163798-C-G is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGIX	NM_024859.4	c.65C>G	p.Pro22Arg	missense_variant	Exon 2 of 6	ENST00000595224.6	NP_079135.3
MAGIX	NM_001099681.2	c.65C>G	p.Pro22Arg	missense_variant	Exon 2 of 5		NP_001093151.2
MAGIX	NM_001099682.2	c.65C>G	p.Pro22Arg	missense_variant	Exon 2 of 5		NP_001093152.2
MAGIX	NM_001395401.1	c.-186C>G		5_prime_UTR_variant	Exon 2 of 5		NP_001382330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGIX	ENST00000595224.6	c.65C>G	p.Pro22Arg	missense_variant	Exon 2 of 6	5	NM_024859.4	ENSP00000471299.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000267 AC: 25 AN: 935748 Hom.: 0 Cov.: 30 AF XY: 0.0000271 AC XY: 8 AN XY: 295712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000438

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000209

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 06, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0020
DANN	Benign	0.30
DEOGEN2	Benign	0.027	T;T;T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;.;N
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.080
MutPred		0.30		Gain of MoRF binding (P = 0.0081);Gain of MoRF binding (P = 0.0081);Gain of MoRF binding (P = 0.0081);
MVP		0.12
ClinPred		0.096	T
GERP RS		-5.7
Varity_R		0.046
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs1194432565; hg19: chrX-49020136;