Genetic Variant NM_016249.4:c.586G>T (chrX-142203402-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016249.4(MAGEC2):c.586G>T(p.Ala196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,541 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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. A196T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEC2
NM_016249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.401

Variant links:

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]

MAGEC2 links:

ENSG00000288098 (HGNC:):

ENSG00000288098 links:

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ACMG classification

Classification made for transcript

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=0.21340752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC2	NM_016249.4 link	c.586G>T	p.Ala196Ser	missense_variant	Exon 3 of 3	ENST00000247452.4	NP_057333.1	Q9UBF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC2	ENST00000247452.4 link	c.586G>T	p.Ala196Ser	missense_variant	Exon 3 of 3	1	NM_016249.4	ENSP00000354660.2		Q9UBF1
ENSG00000288098	ENST00000664519.1 link	n.300+7618C>A		intron_variant	Intron 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111392

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33586

show subpopulations

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098149

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363505

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000898

AC:

AN:

111392

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.4

DANN

Benign

0.91

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.12

M_CAP

Benign

0.0025

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.43

PrimateAI

Benign

0.30

PROVEAN

Benign

1.0

REVEL

Benign

0.026

Sift

Benign

0.089

Sift4G

Benign

0.27

Polyphen

0.0040

Vest4

0.050

MutPred

0.48

Gain of sheet (P = 0.0827);

MVP

0.11

MPC

0.010

ClinPred

0.054

GERP RS

-2.0

Varity_R

0.055

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over