6-89198154-G-C

Variant names:

• chr6-89198154-G-C
• rs422751
• NM_002042.5:c.438C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002042.5(GABRR1):​c.438C>G​(p.Asp146Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: GABRR1 NM_002042.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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]

ACMG classification

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, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.438C>G	p.Asp146Glu	missense_variant	Exon 5 of 10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.438C>G	p.Asp146Glu	missense_variant	Exon 5 of 10	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.76	D
LIST_S2	Pathogenic	0.99	D;D;.;D;.
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D;D;.;.;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;D;.;.;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.98	D;P;.;.;.
Vest4		0.82
MutPred		0.58		Loss of MoRF binding (P = 0.1185);.;.;.;.;
MVP		0.82
MPC		0.74
ClinPred		0.99	D
GERP RS		-2.4
Varity_R		0.59
gMVP		0.41

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

Other links and lift over

dbSNP: rs422751; hg19: chr6-89907873;