Variant X-152736217-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001166387.4(MAGEA12):c.56A>G(p.Gln19Arg) 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 1,098,153 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEA12
NM_001166387.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

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

CSAG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038305044).

BP6

Variant X-152736217-A-G is Benign according to our data. Variant chrX-152736217-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2218374.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAGEA12	NM_001166387.4 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	3/3	ENST00000393869.8
CSAG4	NR_073432.1 linkuse as main transcript	n.33+2358A>G		intron_variant, non_coding_transcript_variant
MAGEA12	NM_001166386.3 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	3/3
MAGEA12	NM_005367.7 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAGEA12	ENST00000393869.8 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	3/3	2	NM_001166387.4	P1
MAGEA12	ENST00000357916.8 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	2/2	1		P1
MAGEA12	ENST00000393900.4 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	3/3	1		P1
CSAG4	ENST00000361201.8 linkuse as main transcript	n.33+2358A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183030

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67642

show subpopulations

Gnomad AFR exome

AF:

0.0000766

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098153

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363529

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

Cov.:

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

Oct 12, 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

0.065

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.066

DANN

Benign

0.41

DEOGEN2

Benign

0.0092

T;T;T

LIST_S2

Benign

0.36

T;.;.

MetaRNN

Benign

0.038

T;T;T

PROVEAN

Uncertain

-2.5

D;D;D

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Vest4

0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.34

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