rs176024

chrX-141895278-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_138702.1(MAGEC3):c.919G>A(p.Ala307Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.87 (29987 hom., 26526 hem., cov: 21)
  • Exomes 𝑓: 0.91 (312362 hom. 327986 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC3 NM_138702.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6467494E-6).
• BS2: High Homozygotes in GnomAd at 30002 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC3	NM_138702.1	c.919G>A	p.Ala307Thr	missense_variant	5/8	ENST00000298296.1
MAGEC3	NM_177456.2	c.-369G>A		5_prime_UTR_variant	2/5
MAGEC3	XM_011531267.4			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC3	ENST00000298296.1	c.919G>A	p.Ala307Thr	missense_variant	5/8	1	NM_138702.1	P2
MAGEC3	ENST00000443323.2	c.-118-1153G>A		intron_variant		1		A2
MAGEC3	ENST00000544766.5	c.-369G>A		5_prime_UTR_variant	2/5	5		A2
MAGEC3	ENST00000483584.5	n.159G>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.867 AC: 94184 AN: 108690 Hom.: 30002 Cov.: 21 AF XY: 0.852 AC XY: 26488 AN XY: 31072

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.856

GnomAD3 exomes AF: 0.837 AC: 152717 AN: 182357 Hom.: 41786 AF XY: 0.837 AC XY: 56032 AN XY: 66913

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.736

Gnomad ASJ exome AF: 0.949

Gnomad EAS exome AF: 0.476

Gnomad SAS exome AF: 0.671

Gnomad FIN exome AF: 0.912

Gnomad NFE exome AF: 0.950

Gnomad OTH exome AF: 0.877

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.912 AC: 1001001 AN: 1097164 Hom.: 312362 Cov.: 43 AF XY: 0.904 AC XY: 327986 AN XY: 362648

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.952

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.883

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.866 AC: 94195 AN: 108733 Hom.: 29987 Cov.: 21 AF XY: 0.852 AC XY: 26526 AN XY: 31125

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.848

Alfa AF: 0.925 Hom.: 134332

Bravo AF: 0.855

TwinsUK AF: 0.954 AC: 3536

ALSPAC AF: 0.957 AC: 2764

ESP6500AA AF: 0.808 AC: 3099

ESP6500EA AF: 0.952 AC: 6404

ExAC AF: 0.840 AC: 101989

EpiCase AF: 0.951

EpiControl AF: 0.948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-1.0	T
BayesDel_noAF	Benign	-1.1
Cadd	Benign	11
Dann	Benign	0.31
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Benign	0.00086	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.51	N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.015
Sift	Benign	0.21	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.035
MPC		0.020
ClinPred		0.0029	T
GERP RS		0.0071
Varity_R		0.035
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.78		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.78		Position offset: 10

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

Publications

LitVar

Other links and lift over

dbSNP: rs176024; hg19: chrX-140983064; COSMIC: COSV53579977; COSMIC: COSV53579977;