X-142203342-C-G

Variant names:

• chrX-142203342-C-G
• rs1165544744
• NM_016249.4:c.646G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016249.4(MAGEC2):​c.646G>C​(p.Asp216His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,139 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D216N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MAGEC2 NM_016249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047194302).

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.646G>C	p.Asp216His	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.646G>C	p.Asp216His	missense	Exon 3 of 3	ENSP00000354660.2	Q9UBF1
	ENSG00000288098	ENST00000664519.1		n.300+7558C>G		intron	N/A
	ENSG00000288098	ENST00000842232.1		n.78+7558C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098139 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 363493

African (AFR) AF: 0.00 AC: 0 AN: 26402

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842069

Other (OTH) AF: 0.00 AC: 0 AN: 46092

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.12
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.25
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.026
Sift	Benign	0.46	T
Sift4G	Benign	0.51	T
Polyphen		0.15	B
Vest4		0.098
MutPred		0.34		Gain of glycosylation at T215 (P = 0.1166)
MVP		0.13
MPC		0.054
ClinPred		0.071	T
GERP RS		-2.0
Varity_R		0.040
gMVP		0.22
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: rs1165544744; hg19: chrX-141291128;