5-170789190-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014211.3(GABRP):​c.115C>T​(p.Pro39Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

GABRP
NM_014211.3 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.02
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRPNM_014211.3 linkc.115C>T p.Pro39Ser missense_variant Exon 3 of 10 ENST00000265294.9 NP_055026.1
GABRPNM_001291985.2 linkc.115C>T p.Pro39Ser missense_variant Exon 3 of 9 NP_001278914.1 O00591B4DTP4E7EWG0
GABRPXM_024446012.2 linkc.115C>T p.Pro39Ser missense_variant Exon 3 of 10 XP_024301780.1
GABRPXM_005265872.2 linkc.-66+522C>T intron_variant Intron 1 of 7 XP_005265929.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRPENST00000265294.9 linkc.115C>T p.Pro39Ser missense_variant Exon 3 of 10 1 NM_014211.3 ENSP00000265294.4 O00591

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251470
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135910
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:
0.0000315
AC:
46
AN:
1461870
Hom.:
0
Cov.:
30
AF XY:
0.0000330
AC XY:
24
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.35
.;.;.;.;T;.;T;.;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D;D;D;.;D;D;D;D
M_CAP
Uncertain
0.095
D
MetaRNN
Uncertain
0.46
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.074
T
MutationAssessor
Benign
0.55
.;.;.;.;N;.;N;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.5
D;D;D;D;N;D;N;D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0030
D;D;D;T;D;D;D;D;D
Sift4G
Benign
0.16
T;T;D;T;T;D;T;T;T
Polyphen
0.99, 1.0
.;.;.;.;D;.;D;D;.
Vest4
0.45, 0.48, 0.43, 0.42
MutPred
0.37
Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);
MVP
0.94
MPC
0.29
ClinPred
0.91
D
GERP RS
5.1
Varity_R
0.20
gMVP
0.59

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: rs778878134; hg19: chr5-170216194; API