rs1179127435

Variant names:

• chrX-152701141-C-G
• rs1179127435
• NM_005362.4:c.309C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-152701141-C-G
• chrX-152701141-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_005362.4(MAGEA3):​c.309C>G​(p.Ser103Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,621 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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. S103S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: MAGEA3 NM_005362.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.639).
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.309C>G	p.Ser103Ser	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.309C>G	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.309C>G	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.309C>G	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095621 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 2 AN XY: 361367

African (AFR) AF: 0.00 AC: 0 AN: 26365

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19340

East Asian (EAS) AF: 0.00 AC: 0 AN: 30112

South Asian (SAS) AF: 0.00 AC: 0 AN: 53976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840291

Other (OTH) AF: 0.00 AC: 0 AN: 46005

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.64
PhyloP100		-1.0

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: rs1179127435;