6-89198098-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002042.5(GABRR1):c.494G>A(p.Arg165His) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
GABRR1
NM_002042.5 missense
NM_002042.5 missense
Scores
5
6
8
Clinical Significance
Conservation
PhyloP100: 6.13
Genes affected
GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRR1 | NM_002042.5 | c.494G>A | p.Arg165His | missense_variant | 5/10 | ENST00000454853.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRR1 | ENST00000454853.7 | c.494G>A | p.Arg165His | missense_variant | 5/10 | 1 | NM_002042.5 | P1 | |
GABRR1 | ENST00000435811.5 | c.443G>A | p.Arg148His | missense_variant | 4/9 | 2 | |||
GABRR1 | ENST00000369451.7 | c.233G>A | p.Arg78His | missense_variant | 7/12 | 5 | |||
GABRR1 | ENST00000457434.1 | c.*455G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152054Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251418Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135898
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727246
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
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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 | Sep 22, 2022 | The c.494G>A (p.R165H) alteration is located in exon 5 (coding exon 5) of the GABRR1 gene. This alteration results from a G to A substitution at nucleotide position 494, causing the arginine (R) at amino acid position 165 to be replaced by a histidine (H). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.;.;N
REVEL
Uncertain
Sift
Benign
T;T;.;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0808);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
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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