rs1248162986

Variant names:

• chrX-152701175-G-A
• rs1248162986
• NM_005362.4:c.343G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-152701175-G-A
• chrX-152701175-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_005362.4(MAGEA3):​c.343G>A​(p.Glu115Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., 7 hem., cov: 21)
  • Exomes 𝑓: 0.00075 (6 hom. 446 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEA3 NM_005362.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.509
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1510337).
• BP6: Variant X-152701175-G-A is Benign according to our data. Variant chrX-152701175-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 726564.Status of the report is criteria_provided_single_submitter, 1 stars.

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.343G>A	p.Glu115Lys	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.343G>A	p.Glu115Lys	missense	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.343G>A	p.Glu115Lys	missense	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.343G>A	p.Glu115Lys	missense	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes AF: 0.000580 AC: 64 AN: 110334 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000285

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00377

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.00135

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000750 AC: 821 AN: 1094811 Hom.: 6 Cov.: 31 AF XY: 0.00123 AC XY: 446 AN XY: 361223

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

African (AFR) AF: 0.000228 AC: 6 AN: 26364

American (AMR) AF: 0.000228 AC: 8 AN: 35146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00588 AC: 177 AN: 30104

South Asian (SAS) AF: 0.00243 AC: 131 AN: 53944

European-Finnish (FIN) AF: 0.000149 AC: 6 AN: 40290

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4119

European-Non Finnish (NFE) AF: 0.000535 AC: 449 AN: 839535

Other (OTH) AF: 0.000849 AC: 39 AN: 45960

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000580 AC: 64 AN: 110390 Hom.: 0 Cov.: 21 AF XY: 0.000212 AC XY: 7 AN XY: 32990

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

African (AFR) AF: 0.000328 AC: 10 AN: 30459

American (AMR) AF: 0.000285 AC: 3 AN: 10532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2611

East Asian (EAS) AF: 0.00378 AC: 13 AN: 3441

South Asian (SAS) AF: 0.00354 AC: 9 AN: 2543

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5955

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.000515 AC: 27 AN: 52453

Other (OTH) AF: 0.00133 AC: 2 AN: 1505

⚠️ 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: 0.00138 Hom.: 15

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
AlphaMissense	Benign	0.17
CADD	Benign	7.5
DEOGEN2	Benign	0.34	T
LIST_S2	Benign	0.065	T
MetaRNN	Benign	0.15	T
PhyloP100		0.51
PROVEAN	Uncertain	-2.6	D
Sift	Benign	0.66	T
Sift4G	Benign	0.20	T
Vest4		0.19
gMVP		0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1248162986;