Variant X-152736853-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001166387.4(MAGEA12):c.692C>G(p.Ser231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,087 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

MAGEA12
NM_001166387.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

MAGEA12 (HGNC:6799): (MAGE family member A12) This gene is closely related to several other genes clustered on chromosome X. These genes may be overexpressed in tumors. Multiple alternatively spliced variants encoding the same protein have been identified. [provided by RefSeq, Jun 2014]

MAGEA12 links:

CSAG4 (HGNC:):

CSAG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06772104).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA12	NM_001166387.4 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	3/3	ENST00000393869.8	NP_001159859.1	P43365
MAGEA12	NM_001166386.3 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	3/3		NP_001159858.1	P43365
MAGEA12	NM_005367.7 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	2/2		NP_005358.2	P43365
CSAG4	NR_073432.1 linkuse as main transcript	n.34-2830C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAGEA12	ENST00000393869.8 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	3/3	2	NM_001166387.4	ENSP00000377447.3	P43365
MAGEA12	ENST00000357916.8 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	2/2	1		ENSP00000350592.4	P43365
MAGEA12	ENST00000393900.4 linkuse as main transcript	c.692C>G	p.Ser231Cys	missense_variant	3/3	1		ENSP00000377478.3	P43365
CSAG4	ENST00000361201.8 linkuse as main transcript	n.34-2830C>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111937

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34087

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182175

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67027

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000455

AC:

AN:

1098150

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111937

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34087

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:

0.0000188

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.692C>G (p.S231C) alteration is located in exon 3 (coding exon 1) of the MAGEA12 gene. This alteration results from a C to G substitution at nucleotide position 692, causing the serine (S) at amino acid position 231 to be replaced by a cysteine (C). 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

0.068

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.6

DANN

Benign

0.95

DEOGEN2

Benign

0.0016

T;T;T

LIST_S2

Benign

0.20

T;.;.

MetaRNN

Benign

0.068

T;T;T

PROVEAN

Benign

-0.19

N;N;N

Sift

Uncertain

0.029

D;D;D

Sift4G

Benign

0.099

T;T;T

Vest4

0.12

gMVP

0.87

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over