chrX-14532285-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002063.4(GLRA2):āc.115T>Cā(p.Ser39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,077 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes š: 0.0000019 ( 0 hom. 1 hem. )
Consequence
GLRA2
NM_002063.4 missense
NM_002063.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 1.44
Genes affected
GLRA2 (HGNC:4327): (glycine receptor alpha 2) The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.15941074).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLRA2 | NM_002063.4 | c.115T>C | p.Ser39Pro | missense_variant | 2/9 | ENST00000218075.9 | NP_002054.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLRA2 | ENST00000218075.9 | c.115T>C | p.Ser39Pro | missense_variant | 2/9 | 1 | NM_002063.4 | ENSP00000218075 | A1 | |
GLRA2 | ENST00000355020.9 | c.115T>C | p.Ser39Pro | missense_variant | 2/9 | 1 | ENSP00000347123 | P4 | ||
GLRA2 | ENST00000415367.2 | n.366T>C | non_coding_transcript_exon_variant | 2/9 | 3 | |||||
GLRA2 | ENST00000443437.6 | c.*82T>C | 3_prime_UTR_variant, NMD_transcript_variant | 4/11 | 2 | ENSP00000387756 |
Frequencies
GnomAD3 genomes AF: 0.00000895 AC: 1AN: 111770Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 33990
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GnomAD4 exome AF: 0.00000186 AC: 2AN: 1077307Hom.: 0 Cov.: 23 AF XY: 0.00000290 AC XY: 1AN XY: 344715
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GnomAD4 genome AF: 0.00000895 AC: 1AN: 111770Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 33990
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | The c.115T>C (p.S39P) alteration is located in exon 2 (coding exon 2) of the GLRA2 gene. This alteration results from a T to C substitution at nucleotide position 115, causing the serine (S) at amino acid position 39 to be replaced by a proline (P). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MutPred
Gain of catalytic residue at P38 (P = 0.0133);Gain of catalytic residue at P38 (P = 0.0133);.;
MVP
MPC
ClinPred
T
GERP RS
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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