X-142202918-A-G

Position:

• chrX-142202918-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016249.4(MAGEC2):​c.1070T>C​(p.Met357Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGEC2 NM_016249.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.191

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08449119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC2	NM_016249.4	c.1070T>C	p.Met357Thr	missense_variant	3/3	ENST00000247452.4	NP_057333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC2	ENST00000247452.4	c.1070T>C	p.Met357Thr	missense_variant	3/3	1	NM_016249.4	ENSP00000354660	P1
	ENST00000664519.1	n.300+7134A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.1070T>C (p.M357T) alteration is located in exon 3 (coding exon 1) of the MAGEC2 gene. This alteration results from a T to C substitution at nucleotide position 1070, causing the methionine (M) at amino acid position 357 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.23
DEOGEN2	Benign	0.046	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.040	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.021
Sift	Benign	0.12	T
Sift4G	Benign	0.32	T
Polyphen		0.055	B
Vest4		0.25
MutPred		0.23		Gain of glycosylation at M357 (P = 0.026);
MVP		0.043
MPC		0.013
ClinPred		0.037	T
GERP RS		-2.1
Varity_R		0.083
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1931164667; hg19: chrX-141290704;