6-89180447-C-A

Variant names:

• chr6-89180447-C-A
• rs772700915
• NM_002042.5:c.991G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002042.5(GABRR1):​c.991G>T​(p.Val331Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V331M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GABRR1 NM_002042.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.991G>T	p.Val331Leu	missense	Exon 9 of 10	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.940G>T	p.Val314Leu	missense	Exon 8 of 9	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.730G>T	p.Val244Leu	missense	Exon 10 of 11	NP_001243633.1	P24046-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.991G>T	p.Val331Leu	missense	Exon 9 of 10	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.940G>T	p.Val314Leu	missense	Exon 8 of 9	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000369451.7	TSL:5	c.730G>T	p.Val244Leu	missense	Exon 11 of 12	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.56
Sift	Benign	0.42	T
Sift4G	Benign	0.42	T
Polyphen		0.80	P
Vest4		0.63
MutPred		0.61		Loss of glycosylation at T329 (P = 0.1279)
MVP		0.93
MPC		0.91
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.88
Mutation Taster		=35/65	disease causing

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

Other links and lift over

dbSNP: rs772700915; hg19: chr6-89890166;