chrX-141895317-C-T

Position:

• chrX-141895317-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177456.2(MAGEC3):​c.-330C>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 NM_177456.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1	c.958C>T	p.Leu320Leu	synonymous_variant	5/8	ENST00000298296.1	NP_619647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1	c.958C>T	p.Leu320Leu	synonymous_variant	5/8	1	NM_138702.1	ENSP00000298296.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31594 AN: 109437 Hom.: 3870 Cov.: 21 AF XY: 0.264 AC XY: 8411 AN XY: 31805

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

GnomAD3 exomes AF: 0.222 AC: 40612 AN: 183234 Hom.: 3631 AF XY: 0.213 AC XY: 14435 AN XY: 67702

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 SAS exome AF: 0.0842

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

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.0446

Gnomad4 SAS exome AF: 0.0908

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.256

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.277

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs176025; hg19: chrX-140983103; COSMIC: COSV68924354; COSMIC: COSV68924354;