rs176024

Variant names:

• chrX-141895278-G-A
• rs176024
• NM_138702.1:c.919G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-141895278-G-A
• chrX-141895278-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

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.

• 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
• Publications: 24 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC3	NM_138702.1	c.919G>A	p.Ala307Thr	missense_variant	Exon 5 of 8	ENST00000298296.1	NP_619647.1
MAGEC3	NM_177456.2	c.-369G>A		5_prime_UTR_variant	Exon 2 of 5		NP_803251.1
MAGEC3	XM_011531267.4	c.-292G>A		upstream_gene_variant			XP_011529569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1	c.919G>A	p.Ala307Thr	missense_variant	Exon 5 of 8	1	NM_138702.1	ENSP00000298296.1
MAGEC3	ENST00000443323.2	c.-118-1153G>A		intron_variant	Intron 1 of 2	1		ENSP00000438254.1
MAGEC3	ENST00000483584.5	n.159G>A		non_coding_transcript_exon_variant	Exon 2 of 5	5
MAGEC3	ENST00000544766.5	c.-369G>A		5_prime_UTR_variant	Exon 2 of 5	5		ENSP00000440444.1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 94184 AN: 108690 Hom.: 30002 Cov.: 21

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

GnomAD2 exomes AF: 0.837 AC: 152717 AN: 182357 AF XY: 0.837

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 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

African (AFR) AF: 0.801 AC: 21116 AN: 26358

American (AMR) AF: 0.745 AC: 26208 AN: 35167

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 18413 AN: 19345

East Asian (EAS) AF: 0.484 AC: 14590 AN: 30158

South Asian (SAS) AF: 0.677 AC: 36579 AN: 54052

European-Finnish (FIN) AF: 0.917 AC: 37133 AN: 40504

Middle Eastern (MID) AF: 0.887 AC: 3660 AN: 4126

European-Non Finnish (NFE) AF: 0.954 AC: 802662 AN: 841418

Other (OTH) AF: 0.883 AC: 40640 AN: 46036

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

African (AFR) AF: 0.802 AC: 23848 AN: 29752

American (AMR) AF: 0.769 AC: 7873 AN: 10232

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 2470 AN: 2614

East Asian (EAS) AF: 0.470 AC: 1567 AN: 3332

South Asian (SAS) AF: 0.649 AC: 1592 AN: 2452

European-Finnish (FIN) AF: 0.905 AC: 5117 AN: 5654

Middle Eastern (MID) AF: 0.902 AC: 193 AN: 214

European-Non Finnish (NFE) AF: 0.949 AC: 49652 AN: 52344

Other (OTH) AF: 0.848 AC: 1243 AN: 1466

Alfa AF: 0.922 Hom.: 153483

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
PhyloP100		-1.9
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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