X-152766968-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005363.5(MAGEA6):āc.683T>Cā(p.Leu228Ser) 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 1,097,281 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 21)
Exomes š: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
MAGEA6
NM_005363.5 missense
NM_005363.5 missense
Scores
2
3
10
Clinical Significance
Conservation
PhyloP100: 1.77
Genes affected
MAGEA6 (HGNC:6804): (MAGE family member A6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MAGEA6 | ENST00000329342.10 | c.683T>C | p.Leu228Ser | missense_variant | 3/3 | 1 | NM_005363.5 | ENSP00000329199.5 | ||
| MAGEA6 | ENST00000616035.4 | c.683T>C | p.Leu228Ser | missense_variant | 3/3 | 5 | ENSP00000480637.1 | |||
| MAGEA6 | ENST00000457643.1 | c.683T>C | p.Leu228Ser | missense_variant | 4/4 | 3 | ENSP00000401806.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
21
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097281Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362641
GnomAD4 exome
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1
AN:
1097281
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Cov.:
30
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0
AN XY:
362641
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
21
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 | Dec 22, 2023 | The c.683T>C (p.L228S) alteration is located in exon 3 (coding exon 1) of the MAGEA6 gene. This alteration results from a T to C substitution at nucleotide position 683, causing the leucine (L) at amino acid position 228 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;.
Vest4
MutPred
Gain of disorder (P = 0.005);Gain of disorder (P = 0.005);Gain of disorder (P = 0.005);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.