chrX-14581345-G-A
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_002063.4(GLRA2):c.433G>A(p.Val145Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,205,096 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )
Consequence
GLRA2
NM_002063.4 missense
NM_002063.4 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 8.06
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 -1 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLRA2 | NM_002063.4 | c.433G>A | p.Val145Ile | missense_variant | 4/9 | ENST00000218075.9 | NP_002054.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLRA2 | ENST00000218075.9 | c.433G>A | p.Val145Ile | missense_variant | 4/9 | 1 | NM_002063.4 | ENSP00000218075 | A1 | |
GLRA2 | ENST00000355020.9 | c.433G>A | p.Val145Ile | missense_variant | 4/9 | 1 | ENSP00000347123 | P4 | ||
GLRA2 | ENST00000415367.2 | n.684G>A | non_coding_transcript_exon_variant | 4/9 | 3 | |||||
GLRA2 | ENST00000443437.6 | c.*360G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/11 | 2 | ENSP00000387756 |
Frequencies
GnomAD3 genomes AF: 0.00000894 AC: 1AN: 111844Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 33990
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GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183136Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67712
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GnomAD4 exome AF: 0.00000549 AC: 6AN: 1093252Hom.: 0 Cov.: 29 AF XY: 0.00000557 AC XY: 2AN XY: 358760
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GnomAD4 genome AF: 0.00000894 AC: 1AN: 111844Hom.: 0 Cov.: 22 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 | Jul 19, 2023 | The c.433G>A (p.V145I) alteration is located in exon 4 (coding exon 4) of the GLRA2 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the valine (V) at amino acid position 145 to be replaced by an isoleucine (I). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.098, 0.016
.;B;B;.
Vest4
MutPred
0.72
.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP
MPC
1.1
ClinPred
D
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