4-174677277-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006529.4(GLRA3):c.728T>C(p.Ile243Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,604,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
GLRA3
NM_006529.4 missense
NM_006529.4 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 9.18
Genes affected
GLRA3 (HGNC:4328): (glycine receptor alpha 3) This gene encodes a member of the ligand-gated ion channel protein family. The encoded protein is a member of the glycine receptor subfamily. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.922
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRA3 | NM_006529.4 | c.728T>C | p.Ile243Thr | missense_variant | 7/10 | ENST00000274093.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRA3 | ENST00000274093.8 | c.728T>C | p.Ile243Thr | missense_variant | 7/10 | 1 | NM_006529.4 | ||
GLRA3 | ENST00000340217.5 | c.728T>C | p.Ile243Thr | missense_variant | 7/9 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250364Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135302
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GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452526Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 722990
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
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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 | Mar 01, 2024 | The c.728T>C (p.I243T) alteration is located in exon 7 (coding exon 7) of the GLRA3 gene. This alteration results from a T to C substitution at nucleotide position 728, causing the isoleucine (I) at amino acid position 243 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
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