NM_005362.4:c.612C>A

Variant names:

• chrX-152701444-C-A
• rs1556826649
• NM_005362.4:c.612C>A

Variant summary

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

The NM_005362.4(MAGEA3):​c.612C>A​(p.Ile204Ile) 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. Synonymous variant affecting the same amino acid position (i.e. I204I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEA3 NM_005362.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.

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.612C>A	p.Ile204Ile	synonymous	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.612C>A	p.Ile204Ile	synonymous	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.612C>A	p.Ile204Ile	synonymous	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.612C>A	p.Ile204Ile	synonymous	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1096688 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2 AN XY: 362072

African (AFR) AF: 0.00 AC: 0 AN: 26384

American (AMR) AF: 0.0000853 AC: 3 AN: 35154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30158

South Asian (SAS) AF: 0.00 AC: 0 AN: 54007

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40307

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841146

Other (OTH) AF: 0.00 AC: 0 AN: 46046

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.68
DANN	Benign	0.59
PhyloP100		-2.1

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: rs1556826649; hg19: chrX-151869922;