X-142203431-C-A

Variant names:

• chrX-142203431-C-A
• rs748643907
• NM_016249.4:c.557G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016249.4(MAGEC2):​c.557G>T​(p.Arg186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,209,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R186C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000042 (0 hom. 16 hem.)
• Consequence: MAGEC2 NM_016249.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.102
• Publications: 3 publications found

Genes affected

MAGEC2 (HGNC:13574): (MAGE family member C2) This gene is a member of the MAGEC gene family. It is not expressed in normal tissues, except for testis, and is expressed in tumors of various histological types. This gene and the other MAGEC genes are clustered on chromosome Xq26-q27. [provided by RefSeq, Oct 2009]

ENSG00000288098 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09800395).
• BS2: High Hemizygotes in GnomAdExome4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016249.4. 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
	MAGEC2	NM_016249.4	MANE Select	c.557G>T	p.Arg186Leu	missense	Exon 3 of 3	NP_057333.1	Q9UBF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC2	ENST00000247452.4	TSL:1 MANE Select	c.557G>T	p.Arg186Leu	missense	Exon 3 of 3	ENSP00000354660.2	Q9UBF1
	ENSG00000288098	ENST00000664519.1		n.300+7647C>A		intron	N/A
	ENSG00000288098	ENST00000842232.1		n.78+7647C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111662 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 7 AN: 183339 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000419 AC: 46 AN: 1097896 Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 16 AN XY: 363258

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.000240 AC: 13 AN: 54138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.0000380 AC: 32 AN: 841826

Other (OTH) AF: 0.0000217 AC: 1 AN: 46085

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111662 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33850

African (AFR) AF: 0.00 AC: 0 AN: 30663

American (AMR) AF: 0.00 AC: 0 AN: 10618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3503

South Asian (SAS) AF: 0.00 AC: 0 AN: 2610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53088

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.56
DEOGEN2	Benign	0.084	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.062	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.10
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.019
Sift	Benign	0.14	T
Sift4G	Benign	0.49	T
Polyphen		0.029	B
Vest4		0.051
MutPred		0.70		Gain of ubiquitination at K183 (P = 0.0453)
MVP		0.043
MPC		0.018
ClinPred		0.025	T
GERP RS		-0.088
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.39
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs748643907; hg19: chrX-141291217; COSMIC: COSV55999836;