X-2782081-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001141919.2(XG):c.143C>T(p.Pro48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,209,882 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000019 ( 0 hom. 9 hem. )
Consequence
XG
NM_001141919.2 missense
NM_001141919.2 missense
Scores
1
11
Clinical Significance
Conservation
PhyloP100: 1.54
Genes affected
XG (HGNC:12806): (Xg glycoprotein (Xg blood group)) This gene encodes the XG blood group antigen, and is located at the pseudoautosomal boundary on the short (p) arm of chromosome X. The three 5' exons reside in the pseudoautosomal region and the remaining exons within the X-specific end. A truncated copy of this gene is found on the Y chromosome at the pseudoautosomal boundary. It is transcribed, but not expected to make a Y-chromosome specific gene product. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.11434412).
BS2
High Hemizygotes in GnomAdExome4 at 9 BG gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XG | NM_001141919.2 | c.143C>T | p.Pro48Leu | missense_variant | 4/11 | ENST00000644266.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XG | ENST00000644266.2 | c.143C>T | p.Pro48Leu | missense_variant | 4/11 | NM_001141919.2 | |||
XG | ENST00000381174.10 | c.143C>T | p.Pro48Leu | missense_variant | 4/10 | 1 | P1 | ||
XG | ENST00000419513.7 | c.77C>T | p.Pro26Leu | missense_variant | 2/9 | 1 | |||
XG | ENST00000509484.3 | c.77C>T | p.Pro26Leu | missense_variant | 2/8 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000447 AC: 5AN: 111897Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34069
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GnomAD3 exomes AF: 0.0000436 AC: 8AN: 183431Hom.: 0 AF XY: 0.0000442 AC XY: 3AN XY: 67863
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GnomAD4 exome AF: 0.0000191 AC: 21AN: 1097985Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 9AN XY: 363349
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GnomAD4 genome AF: 0.0000447 AC: 5AN: 111897Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34069
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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 | Aug 17, 2022 | The c.143C>T (p.P48L) alteration is located in exon 4 (coding exon 4) of the XG gene. This alteration results from a C to T substitution at nucleotide position 143, causing the proline (P) at amino acid position 48 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
REVEL
Benign
Polyphen
1.0
.;.;D;D
Vest4
0.39
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at