X-149716386-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The ENST00000355220.6(MAGEA11):ā€‹c.900T>Cā€‹(p.Asp300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,210,137 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. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes š‘“: 0.0000082 ( 0 hom. 2 hem. )

Consequence

MAGEA11
ENST00000355220.6 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.124
Variant links:
Genes affected
MAGEA11 (HGNC:6798): (MAGE family member A11) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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 (BayesDel_noAF=-0.93).
BP6
Variant X-149716386-T-C is Benign according to our data. Variant chrX-149716386-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034896.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.124 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAGEA11NM_005366.5 linkuse as main transcriptc.900T>C p.Asp300= synonymous_variant 5/5 ENST00000355220.6 NP_005357.2
MAGEA11NM_001011544.2 linkuse as main transcriptc.813T>C p.Asp271= synonymous_variant 5/5 NP_001011544.1
MAGEA11XM_047442106.1 linkuse as main transcriptc.900T>C p.Asp300= synonymous_variant 8/8 XP_047298062.1
MAGEA11XM_011531164.3 linkuse as main transcriptc.876T>C p.Asp292= synonymous_variant 4/4 XP_011529466.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAGEA11ENST00000355220.6 linkuse as main transcriptc.900T>C p.Asp300= synonymous_variant 5/51 NM_005366.5 ENSP00000347358 P2P43364-1
MAGEA11ENST00000333104.8 linkuse as main transcriptc.813T>C p.Asp271= synonymous_variant 4/45 ENSP00000328177 A2
MAGEA11ENST00000412632.6 linkuse as main transcriptc.813T>C p.Asp271= synonymous_variant 5/52 ENSP00000391496
MAGEA11ENST00000518694.1 linkuse as main transcriptn.2490T>C non_coding_transcript_exon_variant 7/72

Frequencies

GnomAD3 genomes
AF:
0.00000893
AC:
1
AN:
111934
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34100
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:
0.00000545
AC:
1
AN:
183442
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67882
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000820
AC:
9
AN:
1098203
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
2
AN XY:
363559
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:
0.0000107
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000893
AC:
1
AN:
111934
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34100
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
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MAGEA11-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 12, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
1.6
DANN
Benign
0.40

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.

Other links and lift over

dbSNP: rs1557362515; hg19: chrX-148798046; API