chrX-151924132-C-T

Variant names:

• chrX-151924132-C-T
• rs202047929
• NM_001011548.1:c.468C>T

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.468C>T​(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,210,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 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 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000074 (0 hom. 24 hem.)
• Consequence: MAGEA4 NM_001011548.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.04
• 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=-0.84).
• BP6: Variant X-151924132-C-T is Benign according to our data. Variant chrX-151924132-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.04 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 24 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.468C>T	p.Ser156Ser	synonymous	Exon 3 of 3	NP_001011548.1	P43358
	MAGEA4	NM_001011549.1		c.468C>T	p.Ser156Ser	synonymous	Exon 3 of 3	NP_001011549.1	P43358
	MAGEA4	NM_001011550.1		c.468C>T	p.Ser156Ser	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.468C>T	p.Ser156Ser	synonymous	Exon 3 of 3	ENSP00000276344.2	P43358
	MAGEA4	ENST00000360243.6	TSL:1	c.468C>T	p.Ser156Ser	synonymous	Exon 3 of 3	ENSP00000353379.2	P43358
	MAGEA4	ENST00000370335.5	TSL:1	c.468C>T	p.Ser156Ser	synonymous	Exon 3 of 3	ENSP00000359360.1	P43358

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112358 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000563

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000327 AC: 6 AN: 183468 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000216

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000738 AC: 81 AN: 1098187 Hom.: 0 Cov.: 36 AF XY: 0.0000660 AC XY: 24 AN XY: 363551

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000284 AC: 1 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.000265 AC: 8 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000843 AC: 71 AN: 842129

Other (OTH) AF: 0.0000217 AC: 1 AN: 46096

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112413 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34587

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30984

American (AMR) AF: 0.00 AC: 0 AN: 10651

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.000564 AC: 2 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2683

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53252

Other (OTH) AF: 0.00 AC: 0 AN: 1540

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	-0.84
CADD	Benign	0.26
DANN	Benign	0.67
PhyloP100		-3.0
Mutation Taster		=100/0	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: rs202047929; hg19: chrX-151092604; COSMIC: COSV52341649;