chrX-152701444-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005362.4(MAGEA3):​c.612C>T​(p.Ile204Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,208,506 control chromosomes in the GnomAD database, including 180 homozygotes. There are 1,529 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (86 hom., 726 hem., cov: 21)
  • Exomes 𝑓: 0.0027 (94 hom. 803 hem.)
• Consequence: MAGEA3 NM_005362.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-152701444-C-T is Benign according to our data. Variant chrX-152701444-C-T is described in ClinVar as Benign. ClinVar VariationId is 780740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 2735 AN: 111764 Hom.: 86 Cov.: 21

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000283

Gnomad SAS AF: 0.000373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00424

Gnomad NFE AF: 0.000264

Gnomad OTH AF: 0.0212

GnomAD4 exome AF: 0.00269 AC: 2950 AN: 1096687 Hom.: 94 Cov.: 31 AF XY: 0.00222 AC XY: 803 AN XY: 362071

African (AFR) AF: 0.0878 AC: 2317 AN: 26383

American (AMR) AF: 0.00467 AC: 164 AN: 35154

Ashkenazi Jewish (ASJ) AF: 0.0000517 AC: 1 AN: 19354

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30158

South Asian (SAS) AF: 0.000111 AC: 6 AN: 54007

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

Middle Eastern (MID) AF: 0.00968 AC: 40 AN: 4132

European-Non Finnish (NFE) AF: 0.000176 AC: 148 AN: 841146

Other (OTH) AF: 0.00593 AC: 273 AN: 46046

GnomAD4 genome AF: 0.0245 AC: 2739 AN: 111819 Hom.: 86 Cov.: 21 AF XY: 0.0213 AC XY: 726 AN XY: 34045

African (AFR) AF: 0.0840 AC: 2577 AN: 30685

American (AMR) AF: 0.0106 AC: 113 AN: 10675

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.000283 AC: 1 AN: 3529

South Asian (SAS) AF: 0.000374 AC: 1 AN: 2672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6078

Middle Eastern (MID) AF: 0.00465 AC: 1 AN: 215

European-Non Finnish (NFE) AF: 0.000264 AC: 14 AN: 53098

Other (OTH) AF: 0.0209 AC: 32 AN: 1530

Alfa AF: 0.00905 Hom.: 75

Bravo AF: 0.0294

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
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;