X-152701141-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005362.4(MAGEA3):​c.309C>T​(p.Ser103Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 107,388 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 0.0011 (0 hom., 11 hem., cov: 21)
  • Exomes 𝑓: 0.0011 (9 hom. 620 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEA3 NM_005362.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01

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

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.755).
• BP6: Variant X-152701141-C-T is Benign according to our data. Variant chrX-152701141-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 731289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA3	NM_005362.4	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 3	ENST00000370278.4	NP_005353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEA3	ENST00000370278.4	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 3	1	NM_005362.4	ENSP00000359301.3
MAGEA3	ENST00000598245.2	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 3	2		ENSP00000473093.1
MAGEA3	ENST00000417212.5	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 3	2		ENSP00000392758.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 114 AN: 107335 Hom.: 0 Cov.: 21 AF XY: 0.000355 AC XY: 11 AN XY: 30975

Gnomad AFR AF: 0.000571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00236

Gnomad EAS AF: 0.00305

Gnomad SAS AF: 0.00213

Gnomad FIN AF: 0.000523

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00278

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00109 AC: 1196 AN: 1094743 Hom.: 9 Cov.: 31 AF XY: 0.00172 AC XY: 620 AN XY: 361277

Gnomad4 AFR exome AF: 0.000531

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.00269

Gnomad4 EAS exome AF: 0.00409

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.000920

Gnomad4 NFE exome AF: 0.000888

Gnomad4 OTH exome AF: 0.00122

GnomAD4 genome AF: 0.00111 AC: 119 AN: 107388 Hom.: 0 Cov.: 21 AF XY: 0.000354 AC XY: 11 AN XY: 31034

Gnomad4 AFR AF: 0.000570

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00236

Gnomad4 EAS AF: 0.00305

Gnomad4 SAS AF: 0.00213

Gnomad4 FIN AF: 0.000523

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00229 Hom.: 20

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEA3: PM2:Supporting, BP4, BP7 -

Jan 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1179127435; hg19: -;