X-152701141-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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:3
• 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 -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 Benign/Likely_benign. ClinVar VariationId 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

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>T	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>T	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000359301.3	P43357
	MAGEA3	ENST00000598245.2	TSL:2	c.309C>T	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000473093.1	P43357
	MAGEA3	ENST00000933889.1		c.309C>T	p.Ser103Ser	synonymous	Exon 3 of 3	ENSP00000603948.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 114 AN: 107335 Hom.: 0 Cov.: 21

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

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

African (AFR) AF: 0.000531 AC: 14 AN: 26358

American (AMR) AF: 0.00111 AC: 39 AN: 35103

Ashkenazi Jewish (ASJ) AF: 0.00269 AC: 52 AN: 19321

East Asian (EAS) AF: 0.00409 AC: 123 AN: 30066

South Asian (SAS) AF: 0.00226 AC: 122 AN: 53935

European-Finnish (FIN) AF: 0.000920 AC: 37 AN: 40231

Middle Eastern (MID) AF: 0.00170 AC: 7 AN: 4123

European-Non Finnish (NFE) AF: 0.000888 AC: 746 AN: 839642

Other (OTH) AF: 0.00122 AC: 56 AN: 45964

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

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

African (AFR) AF: 0.000570 AC: 17 AN: 29836

American (AMR) AF: 0.00118 AC: 12 AN: 10204

Ashkenazi Jewish (ASJ) AF: 0.00236 AC: 6 AN: 2546

East Asian (EAS) AF: 0.00305 AC: 10 AN: 3274

South Asian (SAS) AF: 0.00213 AC: 5 AN: 2347

European-Finnish (FIN) AF: 0.000523 AC: 3 AN: 5731

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.00112 AC: 57 AN: 51118

Other (OTH) AF: 0.00616 AC: 9 AN: 1460

⚠️ 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: 0.00229 Hom.: 20

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.76
PhyloP100		-1.0
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

Other links and lift over

dbSNP: rs1179127435;