5-170795396-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014211.3(GABRP):āc.429C>Gā(p.Phe143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,028 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 30)
Exomes š: 0.000020 ( 0 hom. )
Consequence
GABRP
NM_014211.3 missense
NM_014211.3 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.778
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRP | NM_014211.3 | c.429C>G | p.Phe143Leu | missense_variant | 5/10 | ENST00000265294.9 | |
GABRP | NM_001291985.2 | c.429C>G | p.Phe143Leu | missense_variant | 5/9 | ||
GABRP | XM_024446012.2 | c.429C>G | p.Phe143Leu | missense_variant | 5/10 | ||
GABRP | XM_005265872.2 | c.192C>G | p.Phe64Leu | missense_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRP | ENST00000265294.9 | c.429C>G | p.Phe143Leu | missense_variant | 5/10 | 1 | NM_014211.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251446Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727236
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74326
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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 | Feb 23, 2023 | The c.429C>G (p.F143L) alteration is located in exon 5 (coding exon 4) of the GABRP gene. This alteration results from a C to G substitution at nucleotide position 429, causing the phenylalanine (F) at amino acid position 143 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;.;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;M;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
1.0, 1.0
.;.;D;D;D;.
Vest4
0.84, 0.83, 0.85, 0.85
MutPred
Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);
MVP
MPC
0.61
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