5-170795396-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014211.3(GABRP):ā€‹c.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

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
Variant links:
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]

Genome browser will be placed here

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
GABRPNM_014211.3 linkuse as main transcriptc.429C>G p.Phe143Leu missense_variant 5/10 ENST00000265294.9
GABRPNM_001291985.2 linkuse as main transcriptc.429C>G p.Phe143Leu missense_variant 5/9
GABRPXM_024446012.2 linkuse as main transcriptc.429C>G p.Phe143Leu missense_variant 5/10
GABRPXM_005265872.2 linkuse as main transcriptc.192C>G p.Phe64Leu missense_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABRPENST00000265294.9 linkuse as main transcriptc.429C>G p.Phe143Leu missense_variant 5/101 NM_014211.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251446
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461874
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsFeb 23, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;.;T;T;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D;D;.;D;D;D
M_CAP
Benign
0.070
D
MetaRNN
Pathogenic
0.78
D;D;D;D;D;D
MetaSVM
Uncertain
-0.062
T
MutationAssessor
Uncertain
2.2
.;.;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-3.1
D;D;D;D;D;D
REVEL
Uncertain
0.59
Sift
Benign
0.22
T;T;T;T;T;T
Sift4G
Benign
0.48
T;T;T;T;T;T
Polyphen
1.0, 1.0
.;.;D;D;D;.
Vest4
0.84, 0.83, 0.85, 0.85
MutPred
0.53
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
0.81
MPC
0.61
ClinPred
0.86
D
GERP RS
4.7
Varity_R
0.33
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776646552; hg19: chr5-170222400; API