NM_001011548.1:c.288A>G

Variant names:

• chrX-151923952-A-G
• rs201418399
• NM_001011548.1:c.288A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001011548.1(MAGEA4):​c.288A>G​(p.Pro96Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,209,870 control chromosomes in the GnomAD database, including 2 homozygotes. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 7 hem., cov: 23)
  • Exomes 𝑓: 0.00015 (2 hom. 62 hem.)
• Consequence: MAGEA4 NM_001011548.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-151923952-A-G is Benign according to our data. Variant chrX-151923952-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2661656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 7 gene

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.288A>G	p.Pro96Pro	synonymous	Exon 3 of 3	NP_001011548.1	P43358
	MAGEA4	NM_001011549.1		c.288A>G	p.Pro96Pro	synonymous	Exon 3 of 3	NP_001011549.1	P43358
	MAGEA4	NM_001011550.1		c.288A>G	p.Pro96Pro	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.288A>G	p.Pro96Pro	synonymous	Exon 3 of 3	ENSP00000276344.2	P43358
	MAGEA4	ENST00000360243.6	TSL:1	c.288A>G	p.Pro96Pro	synonymous	Exon 3 of 3	ENSP00000353379.2	P43358
	MAGEA4	ENST00000370335.5	TSL:1	c.288A>G	p.Pro96Pro	synonymous	Exon 3 of 3	ENSP00000359360.1	P43358

Frequencies

GnomAD3 genomes AF: 0.000160 AC: 18 AN: 112310 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00604

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000318 AC: 58 AN: 182365 AF XY: 0.000254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00666

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000860

Gnomad OTH exome AF: 0.000444

GnomAD4 exome AF: 0.000147 AC: 161 AN: 1097560 Hom.: 2 Cov.: 36 AF XY: 0.000171 AC XY: 62 AN XY: 362978

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35175

Ashkenazi Jewish (ASJ) AF: 0.00631 AC: 122 AN: 19325

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54015

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40355

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4132

European-Non Finnish (NFE) AF: 0.0000226 AC: 19 AN: 841887

Other (OTH) AF: 0.000412 AC: 19 AN: 46074

GnomAD4 genome AF: 0.000160 AC: 18 AN: 112310 Hom.: 0 Cov.: 23 AF XY: 0.000203 AC XY: 7 AN XY: 34470

African (AFR) AF: 0.0000324 AC: 1 AN: 30900

American (AMR) AF: 0.00 AC: 0 AN: 10683

Ashkenazi Jewish (ASJ) AF: 0.00604 AC: 16 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00 AC: 0 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6188

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53204

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.000998 Hom.: 7

Bravo AF: 0.000159

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		-1.7

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: rs201418399; hg19: chrX-151092424; COSMIC: COSV99367479;