X-151924087-C-T

Variant names:

• chrX-151924087-C-T
• rs769617094
• NM_001011548.1:c.423C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001011548.1(MAGEA4):​c.423C>T​(p.Ile141Ile) variant causes a synonymous 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.

• Frequency: Genomes: not found (cov: 24)
• Consequence: MAGEA4 NM_001011548.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 0 publications found

Genes affected

MAGEA4 (HGNC:6802): (MAGE family member A4) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Several variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011548.1. 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
	MAGEA4	NM_001011548.1	MANE Select	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	NP_001011548.1	P43358
	MAGEA4	NM_001011549.1		c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	NP_001011549.1	P43358
	MAGEA4	NM_001011550.1		c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	NP_001011550.1	P43358

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA4	ENST00000276344.6	TSL:2 MANE Select	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	ENSP00000276344.2	P43358
	MAGEA4	ENST00000360243.6	TSL:1	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	ENSP00000353379.2	P43358
	MAGEA4	ENST00000370335.5	TSL:1	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 3	ENSP00000359360.1	P43358

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.16

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: rs769617094; hg19: chrX-151092559;