X-152736673-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001166387.4(MAGEA12):c.512G>C(p.Arg171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,210,161 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000042 ( 0 hom. 22 hem. )

Consequence

MAGEA12
NM_001166387.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

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:20923): (CSAG family member 4 (pseudogene))

CSAG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028735787).

BP6

Variant X-152736673-G-C is Benign according to our data. Variant chrX-152736673-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2365131.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAGEA12	NM_001166387.4 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	3/3	ENST00000393869.8
CSAG4	NR_073432.1 linkuse as main transcript	n.33+2814G>C		intron_variant, non_coding_transcript_variant
MAGEA12	NM_001166386.3 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	3/3
MAGEA12	NM_005367.7 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAGEA12	ENST00000393869.8 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	3/3	2	NM_001166387.4	P1
MAGEA12	ENST00000357916.8 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	2/2	1		P1
MAGEA12	ENST00000393900.4 linkuse as main transcript	c.512G>C	p.Arg171Pro	missense_variant	3/3	1		P1
CSAG4	ENST00000361201.8 linkuse as main transcript	n.33+2814G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000804

AC:

AN:

111937

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34111

show subpopulations

Gnomad AFR

AF:

0.000195

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:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.0000656

AC:

AN:

182968

Hom.:

AF XY:

0.0000889

AC XY:

AN XY:

67500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000419

AC:

AN:

1098224

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

363596

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.0000273

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000804

AC:

AN:

111937

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34111

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000163

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000665

Alfa

AF:

0.000478

Hom.:

Bravo

AF:

0.0000945

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_noAF

Benign

-0.95

Cadd

Benign

0.12

Dann

Benign

0.65

DEOGEN2

Benign

0.019

T;T;T

LIST_S2

Benign

0.28

T;.;.

MetaRNN

Benign

0.029

T;T;T

PROVEAN

Benign

8.1

N;N;N

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Vest4

0.086

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