ENST00000409007.2:c.-253C>T

Variant names:

• chrX-141895317-C-T
• rs176025
• ENST00000409007.2:c.-253C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000409007.2(MAGEC3):​c.-253C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,207,295 control chromosomes in the GnomAD database, including 29,650 homozygotes. There are 97,156 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.

• Frequency:
  • Genomes: 𝑓 0.29 (3870 hom., 8435 hem., cov: 21)
  • Exomes 𝑓: 0.25 (25780 hom. 88721 hem.)
• Consequence: MAGEC3 ENST00000409007.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 5 publications found

Genes affected

MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409007.2. 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
	MAGEC3	NM_138702.1	MANE Select	c.958C>T	p.Leu320Leu	synonymous	Exon 5 of 8	NP_619647.1	Q8TD91-1
	MAGEC3	NM_177456.2		c.-330C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_803251.1	Q8TD91-2
	MAGEC3	NM_177456.2		c.-330C>T		5_prime_UTR	Exon 2 of 5	NP_803251.1	Q8TD91-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC3	ENST00000409007.2	TSL:1	c.-253C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 6	ENSP00000386566.1
	MAGEC3	ENST00000298296.1	TSL:1 MANE Select	c.958C>T	p.Leu320Leu	synonymous	Exon 5 of 8	ENSP00000298296.1	Q8TD91-1
	MAGEC3	ENST00000409007.2	TSL:1	c.-253C>T		5_prime_UTR	Exon 4 of 6	ENSP00000386566.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31594 AN: 109437 Hom.: 3870 Cov.: 21

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.222 AC: 40612 AN: 183234 AF XY: 0.213

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.0511

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.252 AC: 276128 AN: 1097814 Hom.: 25780 Cov.: 46 AF XY: 0.244 AC XY: 88721 AN XY: 363238

African (AFR) AF: 0.446 AC: 11759 AN: 26372

American (AMR) AF: 0.162 AC: 5704 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 6270 AN: 19367

East Asian (EAS) AF: 0.0446 AC: 1347 AN: 30203

South Asian (SAS) AF: 0.0908 AC: 4917 AN: 54129

European-Finnish (FIN) AF: 0.201 AC: 8129 AN: 40513

Middle Eastern (MID) AF: 0.243 AC: 1003 AN: 4133

European-Non Finnish (NFE) AF: 0.268 AC: 225210 AN: 841843

Other (OTH) AF: 0.256 AC: 11789 AN: 46069

GnomAD4 genome AF: 0.289 AC: 31605 AN: 109481 Hom.: 3870 Cov.: 21 AF XY: 0.265 AC XY: 8435 AN XY: 31859

African (AFR) AF: 0.435 AC: 12981 AN: 29844

American (AMR) AF: 0.212 AC: 2193 AN: 10364

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 816 AN: 2618

East Asian (EAS) AF: 0.0483 AC: 165 AN: 3417

South Asian (SAS) AF: 0.0778 AC: 198 AN: 2545

European-Finnish (FIN) AF: 0.190 AC: 1113 AN: 5867

Middle Eastern (MID) AF: 0.310 AC: 66 AN: 213

European-Non Finnish (NFE) AF: 0.258 AC: 13557 AN: 52453

Other (OTH) AF: 0.277 AC: 412 AN: 1487

Alfa AF: 0.274 Hom.: 2525

Bravo AF: 0.302

EpiCase AF: 0.268

EpiControl AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.49
PhyloP100		-2.2
Mutation Taster		=290/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs176025; hg19: chrX-140983103; COSMIC: COSV68924354; COSMIC: COSV68924354;