X-141879368-GCTACACCCTTTCCCTTC-G

Position:

• chrX-141879368-GCTACACCCTTTCCCTTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138702.1(MAGEC3):​c.455_471delACACCCTTTCCCTTCCT​(p.Tyr152fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,193,059 control chromosomes in the GnomAD database, including 590 homozygotes. There are 3,335 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.046 (306 hom., 1231 hem., cov: 20)
  • Exomes 𝑓: 0.0062 (284 hom. 2104 hem.)
• Consequence: MAGEC3 NM_138702.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.487

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 -10 ACMG points.

• BP6: Variant X-141879368-GCTACACCCTTTCCCTTC-G is Benign according to our data. Variant chrX-141879368-GCTACACCCTTTCCCTTC-G is described in ClinVar as [Benign]. Clinvar id is 779000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1	c.455_471delACACCCTTTCCCTTCCT	p.Tyr152fs	frameshift_variant	3/8	ENST00000298296.1	NP_619647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1	c.455_471delACACCCTTTCCCTTCCT	p.Tyr152fs	frameshift_variant	3/8	1	NM_138702.1	ENSP00000298296.1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 5056 AN: 110389 Hom.: 306 Cov.: 20 AF XY: 0.0374 AC XY: 1223 AN XY: 32665

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00858

Gnomad NFE AF: 0.000625

Gnomad OTH AF: 0.0444

GnomAD3 exomes AF: 0.0141 AC: 2136 AN: 151514 Hom.: 123 AF XY: 0.0101 AC XY: 467 AN XY: 46142

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.00841

Gnomad ASJ exome AF: 0.000289

Gnomad EAS exome AF: 0.0000841

Gnomad SAS exome AF: 0.0169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000371

Gnomad OTH exome AF: 0.00865

GnomAD4 exome AF: 0.00617 AC: 6683 AN: 1082626 Hom.: 284 AF XY: 0.00598 AC XY: 2104 AN XY: 352028

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.0000525

Gnomad4 EAS exome AF: 0.0000337

Gnomad4 SAS exome AF: 0.0184

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000295

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0459 AC: 5064 AN: 110433 Hom.: 306 Cov.: 20 AF XY: 0.0376 AC XY: 1231 AN XY: 32721

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000625

Gnomad4 OTH AF: 0.0439

Alfa AF: 0.0256 Hom.: 125

Bravo AF: 0.0551

Asia WGS AF: 0.0130 AC: 33 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372869684; hg19: chrX-140967154;