6-89185409-C-A

Variant names:

• chr6-89185409-C-A
• rs1771872590
• NM_002042.5:c.697G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002042.5(GABRR1):​c.697G>T​(p.Gly233Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GABRR1 NM_002042.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.697G>T	p.Gly233Cys	missense	Exon 7 of 10	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.646G>T	p.Gly216Cys	missense	Exon 6 of 9	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.436G>T	p.Gly146Cys	missense	Exon 8 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.697G>T	p.Gly233Cys	missense	Exon 7 of 10	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.646G>T	p.Gly216Cys	missense	Exon 6 of 9	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000369451.7	TSL:5	c.436G>T	p.Gly146Cys	missense	Exon 9 of 12	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.60		Gain of methylation at K232 (P = 0.0189)
MVP		0.97
MPC		0.95
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.92
gMVP		0.73
Mutation Taster		=16/84	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: rs1771872590; hg19: chr6-89895128;