X-152700915-C-T

Variant names:

• chrX-152700915-C-T
• rs782605651
• NM_005362.4:c.83C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005362.4(MAGEA3):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., 11 hem., cov: 18)
  • Exomes 𝑓: 0.0011 (2 hom. 261 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEA3 NM_005362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0240
• Publications: 4 publications found

Genes affected

MAGEA3 (HGNC:6801): (MAGE family member A3) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060705453).
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005362.4. 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
	MAGEA3	NM_005362.4	MANE Select	c.83C>T	p.Ala28Val	missense	Exon 3 of 3	NP_005353.1	P43357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA3	ENST00000370278.4	TSL:1 MANE Select	c.83C>T	p.Ala28Val	missense	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.83C>T	p.Ala28Val	missense	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.83C>T	p.Ala28Val	missense	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes AF: 0.000717 AC: 71 AN: 99088 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000181 AC: 1 AN: 55311 AF XY: 0.0000637

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000112

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: AS_VQSR AF: 0.00112 AC: 1010 AN: 903598 Hom.: 2 Cov.: 18 AF XY: 0.00102 AC XY: 261 AN XY: 255292

African (AFR) AF: 0.0000952 AC: 2 AN: 21009

American (AMR) AF: 0.000205 AC: 5 AN: 24347

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15645

East Asian (EAS) AF: 0.00 AC: 0 AN: 27552

South Asian (SAS) AF: 0.0000699 AC: 3 AN: 42908

European-Finnish (FIN) AF: 0.000111 AC: 4 AN: 36187

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2506

European-Non Finnish (NFE) AF: 0.00137 AC: 950 AN: 694418

Other (OTH) AF: 0.00118 AC: 46 AN: 39026

GnomAD4 genome AF: 0.000716 AC: 71 AN: 99118 Hom.: 0 Cov.: 18 AF XY: 0.000466 AC XY: 11 AN XY: 23628

African (AFR) AF: 0.0000792 AC: 2 AN: 25263

American (AMR) AF: 0.00 AC: 0 AN: 9118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2478

East Asian (EAS) AF: 0.00 AC: 0 AN: 3218

South Asian (SAS) AF: 0.00 AC: 0 AN: 2032

European-Finnish (FIN) AF: 0.000192 AC: 1 AN: 5201

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.00137 AC: 68 AN: 49667

Other (OTH) AF: 0.00 AC: 0 AN: 1293

Alfa AF: 0.00110 Hom.: 7

ExAC AF: 0.0000134 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.85
DEOGEN2	Benign	0.082	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.024
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
Vest4		0.048
MutPred		0.29		Gain of sheet (P = 0.0344)
MVP		0.63
ClinPred		0.066	T
GERP RS		-0.60
Varity_R		0.10
gMVP		0.15
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: rs782605651; hg19: chrX-151869393; COSMIC: COSV100939031;