X-142203177-T-C

Variant names:

• chrX-142203177-T-C
• rs775969027
• NM_016249.4:c.811A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_016249.4(MAGEC2):​c.811A>G​(p.Arg271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,208,967 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.000029 (0 hom. 13 hem.)
• Consequence: MAGEC2 NM_016249.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.696
• Publications: 0 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40160322).
• BS2: High Hemizygotes in GnomAdExome4 at 13 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.811A>G	p.Arg271Gly	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.811A>G	p.Arg271Gly	missense	Exon 3 of 3	ENSP00000354660.2	Q9UBF1
	ENSG00000288098	ENST00000664519.1		n.300+7393T>C		intron	N/A
	ENSG00000288098	ENST00000842232.1		n.78+7393T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000359 AC: 4 AN: 111267 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000284

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 182859 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000730

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000292 AC: 32 AN: 1097700 Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 13 AN XY: 363104

African (AFR) AF: 0.0000379 AC: 1 AN: 26395

American (AMR) AF: 0.0000852 AC: 3 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19355

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.0000285 AC: 24 AN: 841707

Other (OTH) AF: 0.0000868 AC: 4 AN: 46079

GnomAD4 genome AF: 0.0000359 AC: 4 AN: 111267 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33477

African (AFR) AF: 0.00 AC: 0 AN: 30571

American (AMR) AF: 0.000284 AC: 3 AN: 10547

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3523

South Asian (SAS) AF: 0.00 AC: 0 AN: 2591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52961

Other (OTH) AF: 0.00 AC: 0 AN: 1487

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.70
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.099
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.19	B
Vest4		0.14
MutPred		0.81		Loss of ubiquitination at K276 (P = 0.1037)
MVP		0.082
MPC		0.010
ClinPred		0.77	D
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.49
Mutation Taster		=95/5	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: rs775969027; hg19: chrX-141290963;